Cesium carbonate → HCID 86629673, 화합물

HRID 2041536노트

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HRID 2041536 반응식
[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]

참가 물질

7

반응물 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, 화합물

생성물 1

HCID 86629673HCID 86629673, 화합물수율 49%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

실험 절차

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)+.

후처리

  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)]

출처 및 근거

ORD 기록
ord-fadc1acfbafa420193b0693b2f72c53a
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580780B2

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