(2S)-N-(1-Cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]amino]pentanamide → HCID 11613537, 화합물

HRID 971328노트

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HRID 971328 반응식
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]2([C:10]([O:12]CC)=[O:11])[CH2:9][CH2:8]2)[N:6]=1.[C:15]([C:17]1([NH:20][C:21](=[O:49])[C@H:22]([CH2:44][C:45]([F:48])([CH3:47])[CH3:46])[NH:23][C@@H:24]([C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[C:25]([F:28])([F:27])[F:26])[CH2:19][CH2:18]1)#[N:16]>CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:15]([C:17]1([NH:20][C:21]([C@@H:22]([NH:23][C@@H:24]([C:29]2[CH:30]=[CH:31][C:32]([C:2]3[S:3][CH:4]=[C:5]([C:7]4([C:10]([OH:12])=[O:11])[CH2:8][CH2:9]4)[N:6]=3)=[CH:33][CH:34]=2)[C:25]([F:26])([F:28])[F:27])[CH2:44][C:45]([F:48])([CH3:47])[CH3:46])=[O:49])[CH2:19][CH2:18]1)#[N:16]

참가 물질

6

반응물 2

HCID 59767791(2S)-N-(1-Cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]amino]pentanamideHCID 69338992HCID 69338992, 화합물

생성물 1

HCID 11613537HCID 11613537, 화합물

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6228Dimethylformamide용매HCID 10340Sodium Carbonate용매

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온도
80 °C

실험 절차

A solution of ethyl 1-(2-bromo-1,3-thiazol-4-yl)cyclopropanecarboxylate (166 mg, 1.2 mmol) and N1-(1-cyanocyclopropyl)-4-fluoro-N2-{(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-L-leucinamide (Example 3, Step 3, 250 mg, 0.5 mmol) in DMF (5 mL) and 2M Na2CO3 (0.63 mL) was degassed with a stream of nitrogen for 10 min, then PdCl2(dppf) (41 mg 0.05 mmol) was added and the mixture heated to 80° C. for 8 h. The mixture was cooled and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic phase was washed with brine, dried over MgSO4 and evaporated. Purification by SiO2 chromatography (30% ethyl acetate/hexanes) provided the title compound.

후처리

  1. temperatureThe mixture was cooled
  2. custompartitioned between ethyl acetate and saturated aqueous ammonium chloride
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customPurification by SiO2 chromatography (30% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-b6aad4ee123f45de81cc4ec1ab343d4a
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07312353B2

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