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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
ノート
印刷プレビュー

反応式

HRID 2264923 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-77e0a59c8e7f4f309539f42837fbcb77
出典データセット
uspto-grants-2010_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07855216B2

反応ノート

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