4-(1-Pyrrolidinyl)piperidine → 4-{3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino}-6-methoxy-7-{2-[4-(1-pyrrolidinyl)-1-piperidinyl]ethoxy}-3-quinolinecarbonitrile

HRID 269784Notes

Reaction equation

HRID 269784 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[N:26]([CH3:30])[CH:27]=[CH:28][N:29]=4)=[C:20]([Cl:31])[CH:19]=3)=[C:10]([C:15]#[N:16])[CH:11]=[N:12]2)=[CH:7][C:6]=1[O:32][CH3:33].[N:34]1([CH:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[CH2:38][CH2:37][CH2:36][CH2:35]1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:31][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[S:24][C:25]1[N:26]([CH3:30])[CH:27]=[CH:28][N:29]=1)[NH:17][C:9]1[C:8]2[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:42]3[CH2:43][CH2:44][CH:39]([N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[CH2:40][CH2:41]3)=[C:6]([O:32][CH3:33])[CH:7]=2)[N:12]=[CH:11][C:10]=1[C:15]#[N:16]

Participants

5

Reactant 3

HCID 787034-(1-Pyrrolidinyl)piperidineHCID 516892Sodium BicarbonateHCID 684582127-(2-chloroethoxy)-4-{3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino]-6-methoxy-3-quinolinecarbonitrile

Product 1

HCID 252527244-{3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino}-6-methoxy-7-{2-[4-(1-pyrrolidinyl)-1-piperidinyl]ethoxy}-3-quinolinecarbonitrileYield 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 200 mg (0.40 mmol) of 7-(2-chloroethoxy)-4-{3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino]-6-methoxy-3-quinolinecarbonitrile and 1.5 g (10 mmol) of 4-pyrrolidin-1-yl-piperidine are heated in N,N-dimethylformamide at 85° C. for 5 hours and at 40° C. for 60 hours. The reaction mixture is poured slowly into saturated aqueous sodium bicarbonate to yield a solid which is subsequently filtered off. The crude solid is washed with water, then recrystallized from anhydrous ethyl ether to give 203 mg of 4-{3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino}-6-methoxy-7-{2-[4-(1-pyrrolidinyl)-1-piperidinyl]ethoxy}-3-quinolinecarbonitrile as an off-white solid, mp 127-130° C.

Workup

  1. customto yield a solid which
  2. filtrationis subsequently filtered off
  3. washThe crude solid is washed with water
  4. customrecrystallized from anhydrous ethyl ether

Sources & evidence

ORD record
ord-ba9c2ca79b2d481a827ad889a2c5afd6
Source dataset
uspto-grants-2008_11
Patent number
US07449460B2

Reaction notes

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