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 2275340

反応式

HRID 2275340 の反応式
[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

参加物

6

反応物 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

生成物 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-carboxamide収率 48%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-bf9630e6253d4e7486cb0ce0df9077e2
出典データセット
uspto-grants-2015_09
特許番号
US09127013B2

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