Cesium fluoride → (S)-(3-chloro-5-trifluoromethyl-benzyl)-(7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 507181노트

반응식

HRID 507181 반응식
Br[C:2]1[C:7]2[NH:8][CH2:9][CH2:10][CH2:11][C@H:12]([N:13]([CH2:20][C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([Cl:31])[CH:22]=3)[C:14]3[N:15]=[N:16][N:17]([CH3:19])[N:18]=3)[C:6]=2[CH:5]=[C:4]([CH3:32])[C:3]=1[C:33]([F:36])(F)[F:34].[CH3:37]B(O)O.[F-:41].[Cs+]>O1CCOCC1.C(OCC)(=O)C.[Cl-].[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].[Pd+2]>[Cl:31][C:23]1[CH:22]=[C:21]([CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=1)[CH2:20][N:13]([C@H:12]1[CH2:11][CH2:10][CH2:9][NH:8][C:7]2[C:2]([CH3:37])=[C:3]([C:33]([F:34])([F:36])[F:41])[C:4]([CH3:32])=[CH:5][C:6]1=2)[C:14]1[N:15]=[N:16][N:17]([CH3:19])[N:18]=1

참가 물질

7

반응물 3

HCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 59432411(S)-(9-bromo-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(3-chloro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine

생성물 1

HCID 59432530(S)-(3-chloro-5-trifluoromethyl-benzyl)-(7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine수율 92.4%

시약·촉매·용매 3

HCID 178478644HCID 178478644, 화합물촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

Add a solution of (S)-(9-bromo-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(3-chloro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine (0.39 g, 0.65 mmol) in dioxane (5 mL) to a mixture of methylboronic acid (0.12 g, 1.96 mmol), palladium diphenylphosphinoferrocene dichloride (0.05 g, 0.06 mmol), and cesium fluoride (0.35 g, 2.32 mmol), then purge with nitrogen and stir for 15 min. at room temperature, then at 100° C. for 4 h. After completion, cool the reaction to room temperature, dilute with ethyl acetate (50 mL) and wash with water and brine (10 mL each). Dry the organic layer over sodium sulfate, filter, and remove the solvent under reduced pressure. Purify the residue using flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (0-30% EtOAc in hexane), to provide the title compound as a white solid (0.32 g, 90%). MS (ES+): 533 (M+H).

후처리

  1. custompurge with nitrogen
  2. waitat 100° C. for 4 h
  3. temperatureAfter completion, cool
  4. customthe reaction to room temperature
  5. washwash with water and brine (10 mL each)
  6. dry with materialDry the organic layer over sodium sulfate
  7. filtrationfilter
  8. customremove the solvent under reduced pressure
  9. customPurify the residue
  10. washeluting with hexanes/ethyl acetate (0-30% EtOAc in hexane)

출처 및 근거

ORD 기록
ord-0e19c3b446a44ceba82668720c7e4855
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786108B2

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