Phenyl isocyanate → (R)-1-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3-phenylurea

HRID 588525노트

반응식

HRID 588525 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.[N:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[C:25]=[O:26]>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:25]([NH:24][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:26])=[CH:21][N:22]=2)[N:19]=1

참가 물질

4

반응물 2

HCID 7672Phenyl isocyanateHCID 58334496(R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine

생성물 1

HCID 45273998(R)-1-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3-phenylurea수율 60.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

To a DCM (0.1 mL) solution of (R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine (Preparation B; 6 mg, 0.019 mmol) cooled in an ice bath was added the isocyanatobenzene (2.5 mg, 0.021 mmol) in DCM (0.1 mL) dropwise. The reaction was slowly warmed to ambient temperature and stirred for 1 hour. The reaction was diluted with DCM (2 mL), washed with water, and concentrated. The crude product was purified by silica gel chromatography (eluent=50% EtOAc/hexanes first, then 5% MeOH in DCM) to yield the pure final product as a solid (5 mg, 60%). MS (apci) m/z=435.2 (M+H).

후처리

  1. washwashed with water
  2. concentrationconcentrated
  3. customThe crude product was purified by silica gel chromatography (eluent=50% EtOAc/hexanes first

출처 및 근거

ORD 기록
ord-a2df73b0ab8349a2bca808bbd2ad5f2a
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09227975B2

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