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 524842Notes

Reaction equation

HRID 524842 reaction equation
[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

Participants

4

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-627d879618844f71b0de7a1dc2a23f12
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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