Water → 4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-N-[4-(1H-indol-3-yl)pyrimidin-2-yl]-6-methoxybenzene-1,3-diamine

HRID 1842816

반응식

HRID 1842816 반응식
O.[CH3:2][N:3]([CH3:36])[C@@H:4]1[CH2:8][CH2:7][N:6]([C:9]2[C:14]([N+:15]([O-])=O)=[CH:13][C:12]([NH:18][C:19]3[N:24]=[C:23]([C:25]4[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[NH:27][CH:26]=4)[CH:22]=[CH:21][N:20]=3)=[C:11]([O:34][CH3:35])[CH:10]=2)[CH2:5]1.[NH4+].[Cl-]>[Fe].C(O)C>[CH3:36][N:3]([CH3:2])[C@@H:4]1[CH2:8][CH2:7][N:6]([C:9]2[CH:10]=[C:11]([O:34][CH3:35])[C:12]([NH:18][C:19]3[N:24]=[C:23]([C:25]4[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[NH:27][CH:26]=4)[CH:22]=[CH:21][N:20]=3)=[CH:13][C:14]=2[NH2:15])[CH2:5]1

참가 물질

6

반응물 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71270505N-{4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-(1H-indol-3-yl)pyrimidin-2-amine2회

생성물 1

HCID 866773194-[(3R)-3-dimethylaminopyrrolidin-1-yl]-N-[4-(1H-indol-3-yl)pyrimidin-2-yl]-6-methoxybenzene-1,3-diamine수율 117.2%

시약·촉매·용매 2

HCID 23925Iron촉매HCID 702Ethanol용매

반응 조건

온도
105 °C

실험 절차

Water (4 mL) was added to a stirred mixture of N-{4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-(1H-indol-3-yl)pyrimidin-2-amine (Intermediate 165, 286 mg, 0.60 mmol), iron (202 mg, 3.62 mmol), NH4Cl (22.6 mg, 0.42 mmol) and ethanol (24 mL). The resulting mixture was stirred at 105° C. for 3 h and was then filtered through diatomaceous earth (Celite™) and concentrated in vacuo. Part-purification by ion exchange chromatography, using an SCX column and eluting with 0.35M methanolic ammonia gave the title compound (312 mg, 116%) as a brown gum, which was used without further purification; 1H NMR: 2.13 (2H, d), 2.32 (2H, d), 2.80 (6H, d), 2.87-2.98 (2H, m), 3.19 (2H, d), 3.77 (3H, s), 6.74 (1H, s), 7.17 (4H, ddd), 7.46 (1H, d), 7.56 (1H, s), 7.77 (1H, s), 8.28 (2H, dd), 8.43 (1H, d), 11.76 (1H, s); m/z: ES+ MH+ 444.

후처리

  1. filtrationwas then filtered through diatomaceous earth (Celite™)
  2. concentrationconcentrated in vacuo
  3. customPart-purification by ion exchange chromatography
  4. washeluting with 0.35M methanolic ammonia

출처 및 근거

ORD 기록
ord-e6a6b800d7da4fa9bb0c8afbe9d5958e
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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