Benzotriazol-1-yl 2-amino-6-fluoro-pyrazolo[1,5-a]pyrimidine-3-carboxylate → 2-amino-6-fluoro-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 524842노트

반응식

HRID 524842 반응식
[NH2:1][C:2]1[C:11]([C:12]([O:14]N2C3C=CC=CC=3N=N2)=O)=[C:5]2[N:6]=[CH:7][C:8]([F:10])=[CH:9][N:4]2[N:3]=1.[O:24]1[CH2:27][CH:26]([N:28]2[CH2:33][CH2:32][N:31]([C:34]3[CH:39]=[CH:38][N:37]=[CH:36][C:35]=3[NH2:40])[CH2:30][CH2:29]2)[CH2:25]1>CN1C(=O)CCC1>[NH2:1][C:2]1[C:11]([C:12]([NH:40][C:35]2[CH:36]=[N:37][CH:38]=[CH:39][C:34]=2[N:31]2[CH2:30][CH2:29][N:28]([CH:26]3[CH2:25][O:24][CH2:27]3)[CH2:33][CH2:32]2)=[O:14])=[C:5]2[N:6]=[CH:7][C:8]([F:10])=[CH:9][N:4]2[N:3]=1

참가 물질

4

반응물 2

HCID 86720894Benzotriazol-1-yl 2-amino-6-fluoro-pyrazolo[1,5-a]pyrimidine-3-carboxylateHCID 867208954-[4-(Oxetan-3-yl)piperazin-1-yl]pyridin-3-amine

생성물 1

HCID 867208932-amino-6-fluoro-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
100 °C

실험 절차

To a suspension of benzotriazol-1-yl 2-amino-6-fluoro-pyrazolo[1,5-a]pyrimidine-3-carboxylate 6a (prepared according to methods similar to the one depicted in Preparation 2a) (5 g, 15.62 mmol) in NMP (78.27 mL) was added 4-[4-(oxetan-3-yl)piperazin-1-yl]pyridin-3-amine (prepared according to methods similar to the one depicted in Preparation N-1, described below) (3.660 g, 15.62 mmol) and the resulting mixture heated at 100° C. for 18 hours. The reaction mixture was cooled to RT and then passed through a pre-wetted SCX cartridge (2×50 g cartridge) and the cartridge was washed with methanol. The product was eluted with 2M ammonia in methanol and the eluent was concentrated in vacuo to leave a dark solid that was purified by column chromatography on silica using the ISCO column companion, eluting with DCM and 90:10:1 DCM:MeOH:NH3 (0-100% gradient, 40 g column) Product fractions were combined and concentrated in vacuo to leave the product as a yellow solid which was then recrystallised from methanol to leave pure product as a yellow solid. MS (ES+) 413.2.

후처리

  1. customprepared
  2. customprepared
  3. customdepicted in Preparation N-1
  4. temperatureThe reaction mixture was cooled to RT
  5. washthe cartridge was washed with methanol
  6. washThe product was eluted with 2M ammonia in methanol
  7. concentrationthe eluent was concentrated in vacuo
  8. customto leave a dark solid
  9. customthat was purified by column chromatography on silica using the ISCO column companion
  10. washeluting with DCM and 90:10:1 DCM
  11. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-627d879618844f71b0de7a1dc2a23f12
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340546B2

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