5-Amino-3-phenylisoxazole → tert-butyl (1S,2R)-2-(4-cyano-2-fluoro-5-(3-phenylisoxazol-5-ylamino)phenylamino)cyclohexylcarbamate

HRID 2201091

반응식

HRID 2201091 반응식
Br[C:2]1[C:3]([C:24]#[N:25])=[CH:4][C:5]([F:23])=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:7]=1.[NH2:26][C:27]1[O:31][N:30]=[C:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:28]=1.O.O.O.[O-]C1C=CC=CC=1.[Na+].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>O1CCOCC1.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]>[C:24]([C:3]1[C:2]([NH:26][C:27]2[O:31][N:30]=[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:28]=2)=[CH:7][C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[C:5]([F:23])[CH:4]=1)#[N:25]

참가 물질

7

반응물 4

HCID 2612015-Amino-3-phenylisoxazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23681143Sodium Phenoxide TrihydrateHCID 69283992tert-butyl (1S,2R)-2-(5-bromo-4-cyano-2-fluorophenylamino)cyclohexylcarbamate

생성물 1

HCID 86666162tert-butyl (1S,2R)-2-(4-cyano-2-fluoro-5-(3-phenylisoxazol-5-ylamino)phenylamino)cyclohexylcarbamate수율 20.3%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of tert-butyl (1S,2R)-2-(5-bromo-4-cyano-2-fluorophenylamino)cyclohexylcarbamate (165 mg, 0.400 mmol), 5-amino-3-phenylisoxazole (96 mg, 0.600 mmol), sodium phenoxide trihydrate (136 mg, 0.800 mmol), xantphos (30 mg, 0.051 mmol) and Pd2(dba)3 (30 mg, 0.032 mmol) in dioxane (2 mL) was degassed with Ar, then was heated at 170 C for 30 min by microwave. It was concentrated in vacuo. The residue was purified by HPLC to give tert-butyl (1S,2R)-2-(4-cyano-2-fluoro-5-(3-phenylisoxazol-5-ylamino)phenylamino)cyclohexylcarbamate (40 mg).

후처리

  1. customwas degassed with Ar
  2. temperaturewas heated at 170 C for 30 min by microwave
  3. concentrationIt was concentrated in vacuo
  4. customThe residue was purified by HPLC

출처 및 근거

ORD 기록
ord-a8f09e7f24574bf9b0dd7470762035a7
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359375B2

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