Diisopropylethylamine → 5-Chloro-N2-(2-fluoro-4-(1-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)piperidin-4-yl)-5-methylphenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 536405노트

반응식

HRID 536405 반응식
[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1.Cl[CH2:31][C:32]1[O:36][N:35]=[C:34]([CH:37]([CH3:39])[CH3:38])[N:33]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:17][CH2:18][N:19]([CH2:31][C:32]4[O:36][N:35]=[C:34]([CH:37]([CH3:39])[CH3:38])[N:33]=4)[CH2:20][CH2:21]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 134785095-(Chloromethyl)-3-(propan-2-yl)-1,2,4-oxadiazoleHCID 446126165-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

생성물 1

HCID 582550915-Chloro-N2-(2-fluoro-4-(1-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)piperidin-4-yl)-5-methylphenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (42 mg, 0.1 mmol), 5-(chloromethyl)-3-isopropyl-1,2,4-oxadiazole (17 mg, 0.10 mmol) and DIEA (86 μL, 0.5 mmol) in DMF (1 mL) was stirred at rt overnight. The reaction was diluted with EtOAc (50 mL) and washed with water (2×5 mL). The EtOAc layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica chromatography (50-100% EtOAc in hexanes gradient) to give 5-Chloro-N2-(2-fluoro-4-(1-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)piperidin-4-yl)-5-methylphenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as a white solid; ESMS m/z 540.2 (M+H+).

후처리

  1. washwashed with water (2×5 mL)
  2. dry with materialThe EtOAc layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by silica chromatography (50-100% EtOAc in hexanes gradient)

출처 및 근거

ORD 기록
ord-b575eb21dc994dbca788c59a6d0c5d2d
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859574B2

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