1,1'-Carbonyldiimidazole → (2S,4S)-4-(8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy)-N-(hex-5-enyl)-1-(1H-imidazole-1-carbonyl)-N-methylpyrrolidine-2-carboxamide

HRID 420093Notes

Reaction equation

HRID 420093 reaction equation
Cl.[Cl:2][C:3]1[C:4]([O:37][CH3:38])=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[C:10]([C:13]1[S:14][CH:15]=[C:16]([CH:18]([CH3:20])[CH3:19])[N:17]=1)[CH:9]=[C:8]2[O:21][C@@H:22]1[CH2:26][NH:25][C@H:24]([C:27]([N:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH:35]=[CH2:36])[CH3:30])=[O:28])[CH2:23]1.[C:39](N1C=CN=C1)([N:41]1[CH:45]=[CH:44][N:43]=[CH:42]1)=[O:40]>ClCCl>[Cl:2][C:3]1[C:4]([O:37][CH3:38])=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[C:10]([C:13]1[S:14][CH:15]=[C:16]([CH:18]([CH3:20])[CH3:19])[N:17]=1)[CH:9]=[C:8]2[O:21][C@@H:22]1[CH2:26][N:25]([C:39]([N:41]2[CH:45]=[CH:44][N:43]=[CH:42]2)=[O:40])[C@H:24]([C:27]([N:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH:35]=[CH2:36])[CH3:30])=[O:28])[CH2:23]1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 66650405(2S,4S)-4-(8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy)-N-(hex-5-enyl)-N-methylpyrrolidine-2-carboxamide hydrochloride

Product 1

HCID 66650590(2S,4S)-4-(8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy)-N-(hex-5-enyl)-1-(1H-imidazole-1-carbonyl)-N-methylpyrrolidine-2-carboxamideYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Compound 135 (10 g) was dissolved in anhydrous dichloromethane (20 mL) under argon. 1,1′-Carbonyldiimidazole (2 eq.) was added at room temperature. The reaction mixture was stirred for 45 min. The mixture was diluted with DCM, washed with water, dried over Na2SO4, and concentrated under vacuum. Compound 136 (9.9 g) was recovered as an off-white foam in 99% yield and in 98% purity (HPLC).

Workup

  1. washwashed with water
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customCompound 136 (9.9 g) was recovered as an off-white foam in 99% yield and in 98% purity (HPLC)

Sources & evidence

ORD record
ord-e2bd2437792049e48cf9302f67842b71
Source dataset
uspto-grants-2012_01
Patent number
US08093379B2

Reaction notes

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