Ammonium Chloride → 4-(3-dimethylaminoazetidin-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 1842792노트

반응식

HRID 1842792 반응식
[CH3:1][N:2]([CH3:34])[CH:3]1[CH2:6][N:5]([C:7]2[C:12]([N+:13]([O-])=O)=[CH:11][C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[CH:24]=[N:25][N:26]5[CH2:31][CH2:30][CH2:29][CH2:28][C:27]=45)[CH:20]=[CH:19][N:18]=3)=[C:9]([O:32][CH3:33])[CH:8]=2)[CH2:4]1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[CH3:34][N:2]([CH3:1])[CH:3]1[CH2:4][N:5]([C:7]2[CH:8]=[C:9]([O:32][CH3:33])[C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[CH:24]=[N:25][N:26]5[CH2:31][CH2:30][CH2:29][CH2:28][C:27]=45)[CH:20]=[CH:19][N:18]=3)=[CH:11][C:12]=2[NH2:13])[CH2:6]1

참가 물질

6

반응물 2

HCID 25517Ammonium ChlorideHCID 71240764N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine2회

생성물 1

HCID 866772974-(3-dimethylaminoazetidin-1-yl)-6-methoxy-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine수율 91.2%

시약·촉매·용매 3

HCID 23925Iron촉매HCID 702Ethanol용매HCID 962Water용매

실험 절차

A mixture of N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 140, 130 mg, 0.28 mmol), iron (94 mg, 1.68 mmol) and NH4Cl (10.48 mg, 0.20 mmol) in ethanol (12 mL) and water (4 mL) was heated at reflux for 2.5 h. The mixture was 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 brown gum. Further purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (111 mg, 91%) as a brown gum; 1H NMR (CDCl3): 1.90-1.98 (2H, m), 2.04-2.12 (2H, m), 2.20 (6H, s), 3.08-3.16 (1H, m), 3.23 (2H, t), 3.35 (1H, s), 3.56 (2H, t), 3.84 (3H, s), 3.93 (2H, dd), 4.20 (2H, t), 6.37 (1H, s), 6.76 (1H, d), 7.35 (1H, s), 7.87 (1H, s), 7.95 (1H, s), 8.28 (1H, d); m/z: ES+ MH+ 435.58.

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 brown gum
  8. customFurther purification by FCC
  9. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-ffa569d432f341ad8f424543e297ad26
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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