Diisopropylethylamine → N-(1-cyanocyclopropyl)-2-(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]-3-tritylsulfanylpropionamide

HRID 1696062ノート

反応式

HRID 1696062 の反応式
[F:1][C:2]([F:38])([F:37])[C@@H:3]([NH:11][C@@H:12]([CH2:16][S:17][C:18]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]([OH:15])=O)[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1.Cl.[NH2:40][C:41]1([C:44]#[N:45])[CH2:43][CH2:42]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:44]([C:41]1([NH:40][C:13](=[O:15])[C@@H:12]([NH:11][C@@H:3]([C:4]2[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=2)[C:2]([F:1])([F:37])[F:38])[CH2:16][S:17][C:18]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:43][CH2:42]1)#[N:45]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 575620952(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]-3-tritylsulfanylpropionic acid

生成物 1

HCID 67276819N-(1-cyanocyclopropyl)-2-(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]-3-tritylsulfanylpropionamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 2(R)-[2,2,2-trifluoro-1-(S)-(4-fluorophenyl)ethylamino]-3-tritylsulfanylpropionic acid (21.58 g, 40 mmol; Reference D) and 1-aminocyclopropane-carbonitrile hydrochloride (OmegaChem, 6.16 g, 52 mmol) in DMF (75 mL) at rt was added DIPEA (Aldrich, 21 mL, 120 mmol) followed by solid HATU (ChemPacific, 19.77 g, 52 mmol) in one portion. This dark, homogeneous solution was allowed to stir at rt for 24 h. The reaction mixture was quenched by addition of 10% NaHCO3 (50 mL), followed by water (100 mL) and then extracted with EtOAc and the combined organics were washed with brine. Following drying over anhydrous MgSO4 and concentration in vacuo, the resulting dark oil was chromatographed on silica gel with 3/1 hex/EtOAc elution to afford a diastereomer mixture (ranging from 5.7/1 to 12/1) of N-(1-cyanocyclopropyl)-2-(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]-3-tritylsulfanylpropionamide and (9.83 g) as a yellow solid.

後処理

  1. customThe reaction mixture was quenched by addition of 10% NaHCO3 (50 mL)
  2. extractionextracted with EtOAc
  3. washthe combined organics were washed with brine
  4. dry with materialFollowing drying over anhydrous MgSO4 and concentration in vacuo
  5. customthe resulting dark oil was chromatographed on silica gel with 3/1 hex/EtOAc elution

出典と根拠

ORDレコード
ord-d83b433272a5489d8991e35c2437697b
出典データセット
uspto-grants-2012_04
特許番号
US08163735B2

反応ノート

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