Task Began November 09, 2012 09:11 PM
Explore substances by ID: chloroquine (ID 1)
Answer Type:Substances
Result Count:1
Retrieve reaction information in 1 substance (ID 2) From ID:1
Product
Answer Type:Reactions
Result Count:8
Step Stages Notes Yield
1 1.1R:NaI, S:H2O, rt → 145°C; 25 h
1.2R:H
3
PO
4
, pH 4-4.5; 1 h, reflux
Reactants: 2, Reagents: 2, Solvents: 1,
Steps: 1, Stages: 2
Transformation:
1.Substitution of Aromatic Halides
with Nitrogen Nucleophiles
92%
CASREACT ®: Copyright © 2012 American Chemical Society. All Rights Rerved. CASREACT contains reactions from CAS and from: ZIC/VINITI databa (1974-1999) provided by InfoChem; IN
PI data prior to 1986; Biotransformations databa compiled under the direction of Professor Dr. Klaus Kieslich; organic reactions, portions copyright 1996-2006 John Wiley & Sons, Ltd., John Wiley and Sons, Inc., Organic Reactions Inc., and Organic Synthes Inc. Reproduced under licen. All Rights Rerved.
2. 2 Steps
1
Step Stages Notes Yield
1 1.1R:PBr3, S:DMF,
2 h, rt
1.2R:H2O, 2 h
1.3R:NaHCO3, pH 10
Reactants: 1, Reagents: 3, Solvents: 1,
Steps: 1, Stages: 3
57% Experimental Procedure
General/Typical Procedure: General Procedure A: Bromination of 4-hydroxy-quinolines: To a
suspension of the requisite 4-hydroxy-quinoline (36.2 mmol) in DMF (60 mL) at ambient temperature
was added slowly phosphorous tribromide (37.3 mmol). (In nearly all cas, the reaction mixture
startedout as a suspension and as the full equivalent of phosphorous tribromide was added, went into
solution [with exotherm] and reprecipitated. In some cas, additional DMF was added to allow
stirring.) The resulting mixture was stirred under N2 for .1/2. hour at which point HPLC indicated
consumption of the starting material. The mixture was then quenched with ice chips followed by water,
and allowed to stir for .1/2. hour. The reaction mixture was made basic by the addition of solid
NaHCO3 until the pH was >10 (paper) and filtered. The solid was washed with veral portion of water
and dried in a vac oven (50 °C) for 18 h. In some cas, a solid did not result from the conditions
and the product was extracted into EtOAc, which was washed with veral portions of water, dried
over Na2SO4, filtered, and concentrated to give the title compound. Unless otherwi noted, no
purification was required. 4-Bromo-7-chloro-quinoline, 4d. Yield 57 %. 1H NMR (400 MHz, CDCl3) δ
8.69 (d, J = 4.7 Hz, 1 H), 8.16 (d, J = 9.0 Hz, 1 H), 8.13 (d, J = 2.0 Hz, 1 H), 7.71 (d, J = 4.7 Hz, 1 H),
7.62 (dd, J = 2.1, 9.0 Hz, 1 H); 13C NMR (101 MHz, CDCl3) δ 151.0, 149.3, 136.7, 134.1, 129.0,
128.9, 128.4, 126.5, 125.4; C9H5NBrCl: MH+ calcd. 241.9367; found, 241.9365; HPLC purity @ 254
nm: >99 %.
2
[Reactant]
Step Stages Notes Yield
2 2.1R:K3PO4, C:Pd(OAc)2, C:166330-10-5,
S:Dioxane, 18 h, 85°C
Reactants: 2, Reagents: 1, Catalysts: 2,
Solvents: 1, Steps: 1, Stages: 1
74% Experimental Procedure
General/Typical Procedure: General Procedure for Palladium Catalyzed Amination of 4-
Haloquinolines. An oven-dried 40-mL vial was charged with the 4-haloquinoline (1.0 mmol), Pd(OAc)2
(4 mol %), DPEphos (8 mol %), K3PO4 (2.5 mmol), and the requisite amine (1.5 mmol). An upside-
down 24/40 ptum was placed over the vial and an 18 gauge needle inrted (as a vent) while the
resulting mixture was purged with argon or nitrogen for veral minutes through a cond needle.
Dioxane (4 mL) was introduced through the ptum. The resulting suspension was sparged with
argon or nitrogen for 3-5 min. The vial was quickly capped, then heated to 85 °C (block temp) for 18 h
and cooled. The mixture was adsorbed onto silica gel and purified. Solvent systems for
chromatography were bad on either mixtures of EtOH (contains 10% NH4OH)/CH2Cl2 or THF/
hexanes (THF/hexanes mix contains 2% dimethylethylamine, and THF is inhibitor free). N4-(7-
Chloro-quinolin-4-yl)-N1,N1-diethyl-pentane-1,4-diamine, 7d. Yield 74 %. 1H NMR (400 MHz, CDCl3)
δ 8.50 (d, J = 5.4 Hz, 1 H), 7.92 (d, J = 2.1 Hz, 1 H), 7.63 (d, J = 8.9 Hz, 1 H), 7.33 (dd, J = 2.1, 8.9
Hz, 1 H), 6.40 (d, J = 5.7 Hz, 1 H), 5.20 (d, J = 7.4 Hz, 1 H), 3.73 - 3.66 (m, 1 H), 2.50 (q, J = 7.4 Hz, 4
H), 2.43 (t, J = 7.0 Hz, 2 H), 1.76 - 1.54 (m, 4 H), 1.30 (d, J = 6.7 Hz, 3 H), 0.99 (t, J = 7.1 Hz, 6 H);
13C NMR (101 MHz, CD3OD) δ 152.6, 152.3, 150.2, 136.5, 127.8, 126.0, 124.6, 119.0, 100.1, 55.0,
53.8, 48.0, 36.0, 24.3, 20.8, 11.3; C18H27N3Cl: MH+ calcd. 320.1888; found, 320.1884; HPLC purity @
254 nm: >99 %.
CASREACT ®: Copyright © 2012 American Chemical Society. All Rights Rerved. CASREACT contains reactions from CAS and from: ZIC/VINITI databa (1974-1999) provided by InfoChem; INPI data prior to 1986; Biotransformations databa compiled under the direction of Professor Dr. Klaus Kieslich; organic reactions, portions copyright 1996-2006 John Wiley & Sons, Ltd., John Wiley
and Sons, Inc., Organic Reactions Inc., and Organic Synthes Inc. Reproduced under licen. All Rights Rerved.
3. Single Step
Step Stages Notes Yield 1 1.1R:K3PO4, C:Pd(OAc)2, C:166330-10-5,
S:Dioxane, 18 h, 85°C
Reactants: 2, Reagents: 1, Catalysts: 2,
Solvents: 1, Steps: 1, Stages: 1
Transformation:
1.Substitution of Aromatic Halides
with Nitrogen Nucleophiles
74% Experimental Procedure
General/Typical Procedure: General Procedure for Palladium Catalyzed Amination of 4-Haloquinolines. An oven-dried 40-mL vial was charged with the 4-haloquinoline (1.0 mmol), Pd(OAc)2(4 mol %), DPEphos (8 mol %), K 3PO 4 (2.5 mmol), and the requisite amine (1.5 mmol). An upside-down 24/40 ptum was placed over the vial and an 18 gauge needle inrted (as a vent) while the resulting mixture was purged with argon or nitrogen for veral minutes through a cond needle.Dioxane (4 mL) was introduced through the ptum. The resulting suspension was sparged with
argon or nitrogen for 3-5 min. The vial was quickly capped, then heated to 85 °C (block temp) for 18 h and cooled. The mixture was adsorbed onto silica gel and purified. Solvent systems for
chromatography were bad on either mixtures of EtOH (contains 10% NH 4OH)/CH 2Cl 2 or THF/hexanes (THF/hexanes mix contains 2% dimethylethylamine, and THF is inhibitor free). N
4
-(7-Chloro-quinolin-4-yl)-N
1,N 1-diethyl-pentane-1,4-diamine, 7d. Yield 74 %. 1H NMR (400 MHz, CDCl 3)δ 8.50 (d, J = 5.4 Hz, 1 H), 7.92 (d, J = 2.1 Hz, 1 H), 7.63 (d, J = 8.9 Hz, 1 H), 7.33 (dd, J = 2.1, 8.9Hz, 1 H), 6.40 (d, J = 5.7 Hz, 1 H), 5.20 (d, J = 7.4 Hz, 1 H), 3.73 - 3.66 (m, 1 H), 2.50 (q, J = 7.4 Hz, 4H), 2.43 (t, J = 7.0 Hz, 2 H), 1.76 - 1.54 (m, 4 H), 1.30 (d, J = 6.7 Hz, 3 H), 0.99 (t, J = 7.1 Hz, 6 H);13C NMR (101 MHz, CD 3
OD) δ 152.6, 152.3, 150.2, 136.5, 127.8, 126.0, 124.6, 119.0, 100.1, 55.0,53.8, 48.0, 36.0, 24.3, 20.8, 11.3; C 18H 27N 3Cl: MH + calcd. 320.1888; found, 320.1884; HPLC purity @254 nm: >99 %.
CASREACT ®: Copyright © 2012 American Chemical Society. All Rights Rerved. CASREACT contains reactions from CAS and from: ZIC/VINITI databa (1974-1999) provided by InfoChem; INPI data prior to 1986; Biotransformations databa compiled under the direction of Professor Dr. Klaus Kieslich; organic reactions, portions copyright 1996-2006John Wiley & Sons, Ltd., John Wiley and Sons, Inc., Organic Reactions Inc., and Organic Synthes Inc. Reproduced under licen. All Rights Rerved.4. 2 Steps
1
Step Stages Notes Yield
