Diisopropylethylamine → 5-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842692

반응식

HRID 1842692 반응식
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21](F)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1.Cl.Cl.[CH3:41][N:42]([CH3:47])[CH:43]1[CH2:46][NH:45][CH2:44]1.CN(C)C1CNC1>CC(N(C)C)=O>[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21]([N:45]3[CH2:46][CH:43]([N:42]([CH3:47])[CH3:41])[CH2:44]3)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 10351656N,N-dimethylazetidin-3-amineHCID 22121220N,N-Dimethylazetidin-3-amine--hydrogen chloride (1/2)2회HCID 712393485-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2회

생성물 1

HCID 712407235-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine수율 102.7%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
100 °C

실험 절차

DIPEA (0.341 mL, 1.96 mmol) was added to a mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 20, 254 mg, 0.61 mmol) and N,N-dimethylazetidin-3-amine dihydrochloride (Intermediate 26, 106 mg, 0.61 mmol) in DMA (4 mL) and the mixture was heated to 100° C. for 0.5 h. Further N,N-dimethylazetidin-3-amine (35 mg, 0.19 mmol) was then added and the mixture was heated at 100° C. for a further 2 h and was then left at r.t. overnight. The mixture was purified directly by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia and was concentrated in vacuo onto silica. Purification by FCC, eluting with 0-4% 7N methanolic ammonia in CH2Cl2 gave the title compound (310 mg, 102%) as an orange solid, which was used without further purification; 1H NMR: 2.14 (6H, s), 3.08-3.18 (1H, m), 3.76 (2H, dd), 3.89 (3H, s), 4.02-4.11 (2H, m), 6.28 (1H, s), 7.12 (1H, td), 7.30-7.39 (1H, m), 8.12 (1H, s), 8.37 (1H, br s), 8.42 (1H, s), 8.68 (1H, s), 8.83 (1H, d), 8.94 (1H, d); m/z: ES+ MH+ 495.56.

후처리

  1. temperaturethe mixture was heated at 100° C. for a further 2 h
  2. customThe mixture was purified directly by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. concentrationwas concentrated in vacuo onto silica
  5. customPurification by FCC
  6. washeluting with 0-4% 7N methanolic ammonia in CH2Cl2

출처 및 근거

ORD 기록
ord-20cd47f792db44a6a7f0e1923b52dd8d
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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