1,1'-Carbonyldiimidazole → (R)-N-(5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxyazetidine-1-carboxamide

HRID 537764노트

반응식

HRID 537764 반응식
[F:1][C:2]1([F:24])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[CH:14][C:15]([NH2:16])=[C:9]3[N:8]=2)[C@@H:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[CH2:3]1.C1N=CN([C:30]([N:32]2[CH:36]=N[CH:34]=[CH:33]2)=[O:31])C=1.Cl.N1CC([OH:42])C1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:24][C:2]1([F:1])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[CH:14][C:15]([NH:16][C:30]([N:32]4[CH2:33][CH:34]([OH:42])[CH2:36]4)=[O:31])=[C:9]3[N:8]=2)[C@@H:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[CH2:3]1

참가 물질

6

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 67329839(R)-5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

생성물 1

HCID 58386337(R)-N-(5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxyazetidine-1-carboxamide수율 48%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a DCM (0.7 mL) solution of (R)-5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (25 mg, 0.074 mmol), was added CDI (18 mg, 0.11 mmol) at ambient temperature in one portion. After stirring two hours, azetidin-3-ol hydrochloride (16 mg, 0.15 mmol) was added in one portion, followed by addition of DIEA (0.039 mL, 0.22 mmol). The reaction was stirred overnight, then concentrated, and the residue was directly purified by reverse-phase column chromatography, eluting with 0 to 45% acetonitrile/water to yield the final product as a yellowish oil (15 mg, 48% yield). MS (apci) m/z=433.1 (M+H).

후처리

  1. stirringThe reaction was stirred overnight
  2. concentrationconcentrated
  3. customthe residue was directly purified by reverse-phase column chromatography
  4. washeluting with 0 to 45% acetonitrile/water

출처 및 근거

ORD 기록
ord-e04cd7efd01045ce899c453947053b5e
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865698B2

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