Ammonium Chloride → 4-[(3R)-3-Dimethylaminopyrrolidin-1-yl]-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842787노트

반응식

HRID 1842787 반응식
[CH3:1][N:2]([CH3:35])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:13]([N+:14]([O-])=O)=[CH:12][C:11]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[CH:25]=[N:26][N:27]5[CH2:32][CH2:31][CH2:30][CH2:29][C:28]=45)[CH:21]=[CH:20][N:19]=3)=[C:10]([O:33][CH3:34])[CH:9]=2)[CH2:4]1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[CH3:35][N:2]([CH3:1])[C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([O:33][CH3:34])[C:11]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[CH:25]=[N:26][N:27]5[CH2:32][CH2:31][CH2:30][CH2:29][C:28]=45)[CH:21]=[CH:20][N:19]=3)=[CH:12][C:13]=2[NH2:14])[CH2:4]1

참가 물질

6

반응물 2

HCID 25517Ammonium ChlorideHCID 71270213N-{4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine2회

생성물 1

HCID 866773454-[(3R)-3-Dimethylaminopyrrolidin-1-yl]-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine수율 85%

시약·촉매·용매 3

HCID 23925Iron촉매HCID 702Ethanol용매HCID 962Water용매

실험 절차

A mixture of N-{4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 135, 198.7 mg, 0.42 mmol), iron (139 mg, 2.49 mmol) and NH4Cl (15.6 mg, 0.29 mmol) in ethanol (15 mL) and water (5 mL) was heated at reflux for 2.5 h. The mixture was then allowed to cool to r.t., filtered and concentrated in vacuo. Part-purification by ion exchange chromatography, using an SCX column, eluting with 0.7M methanolic ammonia provided crude material as a yellow gum. Further purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (159 mg, 85%) as a brown foam; 1H NMR (CDCl3): 1.83-1.97 (3H, m), 2.05-2.17 (3H, m), 2.29 (6H, s), 2.83-2.91 (1H, m), 2.98-3.08 (2H, m), 3.15-3.20 (2H, m), 3.24 (2H, t), 3.69 (2H, s), 3.83 (3H, s), 4.20 (2H, t), 6.69 (1H, s), 6.78 (1H, d), 7.45 (1H, s), 7.97 (2H, d), 8.29 (1H, d); m/z: ES+ MH+ 449.65.

후처리

  1. temperaturewas heated
  2. temperatureat reflux for 2.5 h
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPart-purification by ion exchange chromatography
  6. washeluting with 0.7M methanolic ammonia
  7. customprovided crude material as a yellow gum
  8. customFurther purification by FCC
  9. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-b44df91b64ba46c5830479ebf932c129
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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