Sodium Bicarbonate → 6-[4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrazine-2-carboxylic acid dimethylamide

HRID 1693730노트

반응식

HRID 1693730 반응식
[Cl:1][C:2]1[C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][N:5]=[C:4]2[N:17]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:18]=[C:19]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[C:3]=12.[CH3:35][N:36]([CH3:46])[C:37]([C:39]1[CH:44]=[N:43][CH:42]=[C:41](Cl)[N:40]=1)=[O:38].C(=O)(O)[O-].[Na+]>C(#N)C.C1(C)C=CC=CC=1.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:35][N:36]([CH3:46])[C:37]([C:39]1[CH:44]=[N:43][CH:42]=[C:41]([C:7]2[C:2]([Cl:1])=[C:3]3[C:19]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)=[CH:18][N:17]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:34])[CH3:33])[C:4]3=[N:5][CH:6]=2)[N:40]=1)=[O:38]

참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 280647856-chloro-N,N-dimethylpyrazine-2-carboxamideHCID 575375444-chloro-3-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 575376046-[4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrazine-2-carboxylic acid dimethylamide수율 97%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 1140Toluene용매HCID 6342Acetonitrile용매

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온도
110 °C

실험 절차

45 mg (84 mmol) of 4-chloro-3-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine, 5 mg (6 μmol) of (1,1′-bis(diphenylphosphino)ferrocene palladium(II)-dichloride dichloromethane adduct and 25 mg (0.13 mmol) of 6-chloro-pyrazine-2-carboxylic acid dimethylamide were dissolved in a mixture of 1 mL of acetonitrile and 1 mL of toluene. 2 mL of a saturated aqueous solution of sodium bicarbonate was added and the resulting mixture heated in closed vial to 110° C. for 18 h. The aqueous layer was removed and the organic phase evaporated. The residue was purified by flash chromatography on silica gel using a gradient of 10% v/v of methanol in ethyl acetate and hexanes to afford 46 mg (81 μmol, 97%) of 6-[4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrazine-2-carboxylic acid dimethylamide.

후처리

  1. customThe aqueous layer was removed
  2. customthe organic phase evaporated
  3. customThe residue was purified by flash chromatography on silica gel using a gradient of 10% v/v of methanol in ethyl acetate and hexanes

출처 및 근거

ORD 기록
ord-a2c48b74123c4bfca0aeae60f7aa69a0
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158647B2

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