1,2-Ethanediamine, N1,N1,N2-trimethyl- → N1-(2-(Dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl)-2-nitro-1,4-benzenediamine

HRID 1842755

반응식

HRID 1842755 반응식
[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][NH:5][CH3:6].F[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:12]([NH:18][C:19]2[N:24]=[C:23]([C:25]3[C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[N:27]([CH3:34])[CH:26]=3)[CH:22]=[CH:21][N:20]=2)=[C:11]([O:35][CH3:36])[CH:10]=1.ClC1C(C2C3C(=CC=CC=3)N(C)C=2)=NC(NC2C=C([N+]([O-])=O)C(F)=CC=2OC)=NC=1.CCN(C(C)C)C(C)C>FC(F)(F)CO>[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][N:5]([CH3:6])[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:12]([NH:18][C:19]2[N:24]=[C:23]([C:25]3[C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[N:27]([CH3:34])[CH:26]=3)[CH:22]=[CH:21][N:20]=2)=[C:11]([O:35][CH3:36])[CH:10]=1

참가 물질

6

반응물 4

HCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-HCID 81531DiisopropylethylamineHCID 71239058N-(4-fluoro-2-Methoxy-5-nitrophenyl)-4-(1-Methylindol-3-yl)pyriMidin-2-aMineHCID 712392825-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine

생성물 1

HCID 71239349N1-(2-(Dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl)-2-nitro-1,4-benzenediamine수율 62%

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

반응 조건

온도
140 °C

실험 절차

N1,N1,N2-trimethylethane-1,2-diamine (80 mg, 0.79 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 129, (which may be prepared by the method described for Intermediate 87); 350 mg, 0.79 mmol) and DIPEA (0.342 mL, 1.97 mmol) in 2,2,2-trifluoroethanol (5 mL). The mixture was heated in a microwave at 140° C. for 1 h. The cooled reaction mixture was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia and appropriate fractions were combined and concentrated in vacuo onto silica. Purification by FCC, eluting with 0-4% 7N methanolic ammonia in CH2Cl2 gave the title compound (230 mg, 62%) as an orange solid; 1H NMR: 2.16 (6H, s), 2.45-2.49 (2H, t, obscured by DMSO peak), 2.86 (3H, s), 3.26 (2H, t), 3.87 (3H, s), 3.95 (3H, s), 6.85 (1H, s), 7.11 (1H, t), 7.21 (1H, d), 7.25 (1H, t), 7.52 (1H, d), 8.10 (1H, s), 8.31 (1H, d), 8.33 (1H, s), 8.36 (1H, d), 8.62 (1H, s); m/z: ES+ MH+ 476.40.

후처리

  1. custom(which may be prepared by the method
  2. customThe cooled reaction mixture
  3. customwas purified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. concentrationconcentrated in vacuo onto silica
  6. customPurification by FCC
  7. washeluting with 0-4% 7N methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-c8b55d4cf73e40bd86b235d5d0ac17d9
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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