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

HRID 1367125노트

반응식

HRID 1367125 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-51173a88210d425a8aaed2a7841f9635
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893112B2

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