Diisopropylethylamine → N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine

HRID 1842769노트

반응식

HRID 1842769 반응식
Cl.Cl.[CH3:3][N:4]([CH3:9])[CH:5]1[CH2:8][NH:7][CH2:6]1.F[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]2[N:26]=[C:25]([C:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:29]([CH3:36])[CH:28]=3)[C:24]([CH3:37])=[CH:23][N:22]=2)=[C:13]([O:38][CH3:39])[CH:12]=1.CCN(C(C)C)C(C)C>FC(F)(F)CO>[CH3:3][N:4]([CH3:9])[CH:5]1[CH2:8][N:7]([C:11]2[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]3[N:26]=[C:25]([C:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[N:29]([CH3:36])[CH:28]=4)[C:24]([CH3:37])=[CH:23][N:22]=3)=[C:13]([O:38][CH3:39])[CH:12]=2)[CH2:6]1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 22121220N,N-Dimethylazetidin-3-amine--hydrogen chloride (1/2)2회HCID 71239199N-(4-fluoro-2-methoxy-5-nitrophenyl)-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine2회

생성물 1

HCID 71240800N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine수율 71.6%

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

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온도
140 °C

실험 절차

N,N-dimethylazetidin-3-amine (Intermediate 26, 113 mg, 0.65 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-5-methyl-4-(1-methylindol-3-yl)-pyrimidin-2-amine (Intermediate 79, 250 mg, 0.61 mmol) and DIPEA (0.374 mL, 2.15 mmol) in 2,2,2-trifluoroethanol (5 mL). The mixture was heated in a microwave at 140° C. for 1 h. The cooled mixture was purified by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia. Appropriate fractions were combined and concentrated in vacuo onto silica. Further purification by FCC, eluting with 0-4% 7N methanolic ammonia in CH2Cl2 gave the title compound (213 mg, 71%) as an orange foam; 1H NMR: 2.13 (6H, s), 2.37 (3H, s), 3.09-3.16 (1H, m), 3.72 (2H, dd), 3.89 (3H, s), 3.93 (3H, s), 4-4.08 (2H, m), 6.27 (1H, s), 7.04 (1H, t), 7.20-7.26 (1H, m), 7.49 (1H, d), 7.90 (1H, s), 8.03 (1H, s), 8.23 (1H, s), 8.35 (1H, d), 8.46 (1H, s); m/z: ES+ MH+ 488.63.

후처리

  1. customThe cooled mixture was purified by ion exchange chromatography
  2. washeluting with 7M methanolic ammonia
  3. concentrationconcentrated in vacuo onto silica
  4. customFurther purification by FCC
  5. washeluting with 0-4% 7N methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-7702ee9afa9145df8ae81c11e14c6357
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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