Azetidine → (R)-N-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3-hydroxyazetidine-1-carboxamide

HRID 588531노트

반응식

HRID 588531 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH2:23])=[CH:21][N:22]=2)[N:19]=1.C1N=CN([C:29]([N:31]2[CH:35]=N[CH:33]=[CH:32]2)=[O:30])C=1.Cl.N1CC([OH:41])C1.CCN(C(C)C)C(C)C.N1CCC1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH:23][C:29]([N:31]3[CH2:32][CH:33]([OH:41])[CH2:35]3)=[O:30])=[CH:21][N:22]=2)[N:19]=1

참가 물질

7

반응물 5

HCID 10422AzetidineHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 58334496(R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine

생성물 1

HCID 58334488(R)-N-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3-hydroxyazetidine-1-carboxamide수율 99%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a DCM (1 mL) solution of (R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine (Preparation B; 50 mg, 0.16 mmol) was added CDI (39 mg, 0.24 mmol) at ambient temperature in one portion while stirring. After 1 hour stirring, azetidin-3-ol hydrochloride (35 mg, 0.32 mmol) [purchased from Oakwood] was added in one portion, followed by addition of DIEA (83 μL, 0.48 mmol). The reaction mixture was briefly sonicated to help break up the solid particles from azetidine material. After 30 minute stirring at ambient temperature, the reaction was concentrated and directly purified by reverse-phase column chromatography, eluting with 5 to 50% acetonitrile/water to yield the final product as a pale-yellowish solid (65 mg, 99% yield). MS (apci) m/z=415.2 (M+H).

후처리

  1. stirringAfter 1 hour stirring
  2. customThe reaction mixture was briefly sonicated
  3. stirringAfter 30 minute stirring at ambient temperature
  4. concentrationthe reaction was concentrated
  5. customdirectly purified by reverse-phase column chromatography
  6. washeluting with 5 to 50% acetonitrile/water

출처 및 근거

ORD 기록
ord-c1c73d3c8c1348f1819c53770b59c1e4
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09227975B2

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