4-Methylmorpholine → (S)-N-(1-cyanocyclopropyl)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanamide

HRID 1367125ノート

反応式

HRID 1367125 の反応式
[F:1][C:2]([F:28])([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:3][C@H:4]([NH:8][C@@H:9]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:10]([F:13])([F:12])[F:11])[C:5]([OH:7])=O.C(O)(=O)CCCC.Cl.[NH2:37][C:38]1([C:41]#[N:42])[CH2:40][CH2:39]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C>[C:41]([C:38]1([NH:37][C:5](=[O:7])[C@@H:4]([NH:8][C@@H:9]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:10]([F:11])([F:13])[F:12])[CH2:3][C:2]([F:28])([F:1])[CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:40][CH2:39]1)#[N:42]

参加物

8

反応物 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 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 86625058pentanoic acid (S)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanoic acid

生成物 1

HCID 24764492(S)-N-(1-cyanocyclopropyl)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of the above pentanoic acid (S)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanoic acid, (1 mmol), 1-aminocyclopropanecarbonitrile hydrochloride (1.2 mmol), HATU (1.2 mmol) and NMM (4.0 mmol), in DMF, was stirred at RT for 2 hr. Saturated ammonium chloride and ethyl acetate were then added, and the reaction was stirred an additional 20 min at RT, after which product was extracted with ethyl acetate, purified with flash column (30-35% ethyl acetate—hexane), and crystallized with DCM-hexane to give (S)-N-(1′-cyanocyclopropyl)-4,4-difluoro-5-phenyl-2-((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino)pentanamide as a white crystal.

後処理

  1. extractionafter which product was extracted with ethyl acetate
  2. custompurified with flash column (30-35% ethyl acetate—hexane)
  3. customcrystallized with DCM-hexane

出典と根拠

ORDレコード
ord-51173a88210d425a8aaed2a7841f9635
出典データセット
uspto-grants-2011_02
特許番号
US07893112B2

反応ノート

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