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Cesium carbonate → 7-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 2264923
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HRID 2264923 반응식
[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[C:12]([Cl:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH2:17])=[O:5])[CH3:2].[F:18][C:19]1[CH:24]=[C:23]([Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=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[C:12]([Cl:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:17][C:20]1[CH:21]=[CH:22][C:23]([Si:25]([CH3:27])([CH3:26])[CH3:28])=[CH:24][C:19]=1[F:18])=[O:5])[CH3:2]
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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 595964653-Amino-7-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

생성물 1

HCID 59596531
7-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester
수율 74.7%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

실험 절차

A degassed solution of 3-amino-7-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (300 mg, 1.18 mmol), trifluoro-methanesulfonic acid 2-fluoro-4-trimethylsilanyl-phenyl ester (486 mg, 1.53 mmol), Pd2dba3 (54 mg, 0.06 mmol), Xantphos (68 mg, 0.118 mmol) and Cs2CO3 (770 mg, 2.36 mmol) in toluene (10 ml) was heated to reflux then stirred for 16 hours. The reaction mixture was cooled to ambient temperature then filtered through a pad of Celite® washing with toluene. The resultant solution was concentrated in vacuo to give an oil. The oil was purified by flash chromatography (SiO2, cyclohexane:ethyl acetate, gradient 95:5 to 90:10) to provide the title compound as a gum (370 mg, 74%). 1H NMR (CDCl3) 8.64 (1H, s), 8.31 (1H, s), 7.47 (1H, s, br), 7.23 (1H, dd, J=1.5, 110. Hz), 7.10 (1H, dd, J=1.0, 8.0 Hz), 6.97 (1H, t, J=8.0 Hz), 4.42 (2H, q, J=7.0 Hz), 4.35 (3H, s), 1.43 (3H, t, J=7.0 Hz), 0.29 (s, 9H).

후처리

  1. temperatureto reflux
  2. filtrationthen filtered through a pad of Celite®
  3. washwashing with toluene
  4. concentrationThe resultant solution was concentrated in vacuo
  5. customto give an oil
  6. customThe oil was purified by flash chromatography (SiO2, cyclohexane:ethyl acetate, gradient 95:5 to 90:10)

출처 및 근거

ORD 기록
ord-77e0a59c8e7f4f309539f42837fbcb77
출처 데이터셋
uspto-grants-2010_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07855216B2

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