Cesium carbonate → 3-(2-Fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 2264898노트

반응식

HRID 2264898 반응식
[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH2:16])=[O:5])[CH3:2].[F:17][C:18]1[CH:23]=[C:22]([Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:21]=[CH:20][C:19]=1OS(C(F)(F)F)(=O)=O.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:16][C:19]1[CH:20]=[CH:21][C:22]([Si:24]([CH3:26])([CH3:25])[CH3:27])=[CH:23][C:18]=1[F:17])=[O:5])[CH3:2]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59596436Trifluoromethanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl esterHCID 59596525HCID 59596525, 화합물

생성물 1

HCID 595964973-(2-Fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester수율 85.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

실험 절차

3-Amino-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (25 g, 114 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (47.0 g, 149 mmol), Pd2(dba)3 (5.0 g, 5.5 mmol), Xantphos (6.5 g, 11.3 mmol) and cesium carbonate (74.5 g, 228 mmol) were suspended in toluene (500 mL) and the flask evacuated and purged with argon. The reaction mixture was heated at reflux for 18 hours. The mixture was cooled and filtered through Celite® washing through with toluene. The filtrate was evaporated in vacuo and the residue subjected to flash chromatography (SiO2, gradient 0-10% MeOH in DCM) to give the title compound (37.4 g, 85%) as a yellow solid. 1H NMR (CDCl3) 8.79 (1H, d, J=1.1 Hz), 8.39 (1H, d, J=6.1 Hz), 7.60 (1H, s, br), 7.25 (0.5H, s), 7.22 (1H, s), 7.21 (0.5H, d, J=1.0 Hz), 7.14-7.10, (2H, m), 4.42 (2H, q, J=7.0 Hz), 3.97 (3H, s), 1.44 (3H, t, J=7.0 Hz), 0.26 (9H, s).

후처리

  1. customthe flask evacuated
  2. custompurged with argon
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 18 hours
  5. temperatureThe mixture was cooled
  6. filtrationfiltered through Celite®
  7. washwashing through with toluene
  8. customThe filtrate was evaporated in vacuo

출처 및 근거

ORD 기록
ord-9c5078264cc74a2390fd5829aa271a38
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855216B2

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