Cesium carbonate → HCID 86629673、化合物

HRID 2041536ノート

反応式

HRID 2041536 の反応式
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[CH3:27][C:28]([CH3:42])([CH3:41])[CH2:29][C:30]([C:32]1[CH:39]=[CH:38][C:35]([CH2:36][NH2:37])=[C:34]([F:40])[CH:33]=1)=[O:31].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.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]>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:13])([F:15])[F:14])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:37][CH2:36][C:35]1[CH:38]=[CH:39][C:32]([C:30](=[O:31])[CH2:29][C:28]([CH3:42])([CH3:41])[CH3:27])=[CH:33][C:34]=1[F:40]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 57656563HCID 57656563、化合物

生成物 1

HCID 86629673HCID 86629673、化合物収率 49%

試薬・触媒・溶媒 2

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

実験手順

Use a method similar to the General Procedure 5-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (127 mg, 0.3 mmol) with 4-(3,3-dimethyl-butyryl)-2-fluoro-benzylamine (120 mg, 0.54 mmol) by using tris(dibenzylideneacetone)dipalladium(0) (27 mg, 0.03 mmol), BINAP (40 mg, 0.06 mmol) and cesium carbonate (137 mg, 0.42 mmol) in anhydrous toluene (20 mL). Purify by chromatography on silica gel eluting with hexane/EtOAc (19:1 and 9:1) followed by reverse phase HPLC [Zorbax Bonus RP, 5 □M 21.2×100 mm, eluting with water/acetonitrile (0.05% TFA in each) (35:65 to 15:85 gradient over 5 min), flow rate 25 mL/min, UV detector (230 nm)] to give 7-chloro-6-[4-(3,3-dimethyl-butyryl)-2-fluoro-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (72 mg, 49%). MS (ES+) m/z: 499 (M+H)+.

後処理

  1. customPurify by chromatography on silica gel eluting with hexane/EtOAc (19:1 and 9:1)
  2. washeluting with water/acetonitrile (0.05% TFA in each) (35:65 to 15:85 gradient over 5 min), flow rate 25 mL/min, UV detector (230 nm)]

出典と根拠

ORDレコード
ord-fadc1acfbafa420193b0693b2f72c53a
出典データセット
uspto-grants-2013_11
特許番号
US08580780B2

反応ノート

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