(3R)-(+)-3-(Dimethylamino)pyrrolidine → N-[4-[(3R)-3-Dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine

HRID 1842758

반응식

HRID 1842758 반응식
[CH3:1][N:2]([CH3:8])[C@@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.F[C:10]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([NH:19][C:20]2[N:25]=[C:24]([C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]([CH3:35])[CH:27]=3)[CH:23]=[CH:22][N:21]=2)=[C:12]([O:36][CH3:37])[CH:11]=1.ClC1C(C2C3C(=CC=CC=3)N(C)C=2)=NC(NC2C=C([N+]([O-])=O)C(F)=CC=2OC)=NC=1>FC(F)(F)CO>[CH3:1][N:2]([CH3:8])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:10]2[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([NH:19][C:20]3[N:25]=[C:24]([C:26]4[C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[N:28]([CH3:35])[CH:27]=4)[CH:23]=[CH:22][N:21]=3)=[C:12]([O:36][CH3:37])[CH:11]=2)[CH2:4]1

참가 물질

5

반응물 3

HCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidineHCID 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 71270217N-[4-[(3R)-3-Dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine수율 87%

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

반응 조건

온도
140 °C

실험 절차

(3R)—N,N-Dimethylpyrrolidin-3-amine (107 mg, 0.94 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), 0.372 mL, 2.13 mmol) in 2,2,2-trifluoroethanol (5 mL) and 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. 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 (364 mg, 87%) as an orange solid; 1H NMR: 1.74-1.87 (1H, m), 2.11-2.22 (1H, m), 2.21 (6H, s), 2.70-2.81 (1H, m), 3.10-3.21 (2H, m), 3.21-3.28 (1H, m), 3.47 (1H, td), 3.87 (3H, s), 3.95 (3H, s), 6.56 (1H, s), 7.10 (1H, t), 7.18 (1H, d), 7.21-7.27 (1H, m), 7.51 (1H, d), 8.07 (1H, s), 8.29 (1H, d), 8.32 (1H, s), 8.36 (1H, d), 8.54 (1H, s); m/z: ES+ MH+ 488.31.

후처리

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

출처 및 근거

ORD 기록
ord-6e0efccfa1594e7c89757826df247a7c
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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