(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、化合物

HRID 971328ノート

反応式

HRID 971328 の反応式
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]

参加物

6

反応物 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、化合物

生成物 1

HCID 11613537HCID 11613537、化合物

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-b6aad4ee123f45de81cc4ec1ab343d4a
出典データセット
uspto-grants-2007_12
特許番号
US07312353B2

反応ノート

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