Potassium Carbonate → 3-Cyclohexyl-2-[2-(2,4-dimethyl-thiazol-5-yl)-quinolin-6-yl]-1H-indole-6-carboxylic acid methyl ester

HRID 523318Notes

Reaction equation

HRID 523318 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.[CH3:11][C:12]1[S:13][C:14]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23](B(O)O)[CH:24]=3)[N:19]=2)=[C:15]([CH3:17])[N:16]=1.[C:31]([O-:34])([O-])=[O:32].[K+].[K+].[CH2:37](O)C.[C:40]1(C)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>>[CH3:37][O:34][C:31]([C:6]1[CH:5]=[C:4]2[C:9]([C:10]([CH:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)=[C:2]([C:23]3[CH:24]=[C:25]4[C:20](=[CH:21][CH:22]=3)[N:19]=[C:18]([C:14]3[S:13][C:12]([CH3:11])=[N:16][C:15]=3[CH3:17])[CH:27]=[CH:26]4)[NH:3]2)=[CH:8][CH:7]=1)=[O:32]

Participants

5

Reactant 4

HCID 11430Potassium CarbonateHCID 118056312-bromo-1H-indoleHCID 21863594Toluene ethanolHCID 58710276[2-(2,4-Dimethyl-1,3-thiazol-5-yl)quinolin-6-yl]boronic acid

Product 1

HCID 587103273-Cyclohexyl-2-[2-(2,4-dimethyl-thiazol-5-yl)-quinolin-6-yl]-1H-indole-6-carboxylic acid methyl esterYield 67%

Procedure

A mixture of intermediate 1-5 (4.02 g, 12 mmol), 2-(2,4-dimethyl-thiazol-5-yl)-quinoline-6-boronic acid 16-1 (4.58 g, 1.19 eq, synthesized as described in WO2006/076529), K2CO3 (5.13 g, 3.1 eq) and dichloro-bis(triphenylphosphino)-Pd(II) (0.86 g, 0.10 eq) in ethanol/toluene (1:1, 80 mL) was stirred at room temperature under N2 overnight. After concentration under reduced pressure, the reaction mixture was redissolved in ethyl acetate and washed with a 5 M NaHCO3 solution. The obtained yellow precipitate was filtered off, washed with water, then isopropanol to give 4.13 g (67%) of 3-Cyclohexyl-2-[2-(2,4-dimethyl-thiazol-5-yl)-quinolin-6-yl]-1H-indole-6-carboxylic acid methyl ester 16-2 as a yellow solid; m/z=496 (M+H+).

Workup

  1. concentrationAfter concentration under reduced pressure
  2. dissolutionthe reaction mixture was redissolved in ethyl acetate
  3. washwashed with a 5 M NaHCO3 solution
  4. filtrationThe obtained yellow precipitate was filtered off
  5. washwashed with water

Sources & evidence

ORD record
ord-e01e6fa656434af9a0ef7ec34988e810
Source dataset
uspto-grants-2016_05
Patent number
US09334282B2

Reaction notes

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