1,1'-Carbonyldiimidazole → Larotrectinib

HRID 63998ノート

反応式

HRID 63998 の反応式
[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:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([NH2:23])=[C:16]2[N:15]=1.C1N=CN([C:29]([N:31]2[CH:35]=N[CH:33]=[CH:32]2)=[O:30])C=1.N1CC[C@H:38]([OH:41])C1>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:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([NH:23][C:29]([N:31]3[CH2:32][CH2:33][C@H:38]([OH:41])[CH2:35]3)=[O:30])=[C:16]2[N:15]=1

参加物

5

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 2733874(3S)-pyrrolidin-3-olHCID 58386314(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

生成物 1

HCID 46188928Larotrectinib収率 74%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a DCM (0.8 mL) solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 30 mg, 0.095 mmol) was added CDI (31 mg, 0.19 mmol) at ambient temperature in one portion. After stirring two hours, (S)-pyrrolidin-3-ol (17 mg, 0.19 mmol) [purchased from Suven Life Sciences] was added in one portion. The reaction was stirred for 5 minutes before it was concentrated and directly purified by reverse-phase column chromatography, cluting with 0 to 50% acetonitrile/water to yield the final product as a yellowish foamy powder (30 mg, 74% yield). MS (apci) m/z=429.2 (M+H).

後処理

  1. stirringThe reaction was stirred for 5 minutes before it
  2. concentrationwas concentrated
  3. customdirectly purified by reverse-phase column chromatography

出典と根拠

ORDレコード
ord-fb1c29d16dad40df988d0649691dd2e3
出典データセット
uspto-grants-2016_09
特許番号
US09447104B2

反応ノート

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