3-Pyridinemethanamine → N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(pyridin-3-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 529821Notes

Reaction equation

HRID 529821 reaction equation
Br[CH2:2][CH2:3][N:4]1[CH:8]=[C:7]([NH:9][C:10]([C:12]2[CH:13]=[N:14][N:15]3[CH:20]=[CH:19][CH:18]=[N:17][C:16]=23)=[O:11])[C:6]([C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=2[O:28][CH:29]([F:31])[F:30])=[N:5]1.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][NH2:39])[CH:33]=1>CC#N>[Cl:27][C:25]1[CH:24]=[CH:23][C:22]([O:28][CH:29]([F:31])[F:30])=[C:21]([C:6]2[C:7]([NH:9][C:10]([C:12]3[CH:13]=[N:14][N:15]4[CH:20]=[CH:19][CH:18]=[N:17][C:16]=34)=[O:11])=[CH:8][N:4]([CH2:3][CH2:2][NH:39][CH2:38][C:34]3[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=3)[N:5]=2)[CH:26]=1

Participants

4

Reactant 2

HCID 310183-PyridinemethanamineHCID 118522619N-[1-(2-bromoethyl)-3-[5-chloro-2-(difluoromethoxy) phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 118522635N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(pyridin-3-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of N-[1-(2-bromoethyl)-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (150 mg, 0.29 mmol) and pyridin-3-ylmethanamine (158 mg, 1.46 mmol) in MeCN (3 mL) was stirred at 70° C. for 12 h. The resulting mixture was concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-2): Column, C18 silica gel; mobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=30:42 within 12 min; Detector, UV 254 nm. This resulted in 57.7 mg (37%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(pyridin-3-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (Method 25) [M+H]+=539.1, RT=0.87 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.33 (dd, 1H, J=1.5, 6.9 Hz), 8.69-8.67 (m, 2H), 8.50 (d, 1H, J=1.8 Hz), 8.41 (dd, 1H, J=1.5, 4.8 Hz), 8.38 (s, 1H), 7.73-7.70 (m, 1H), 7.61 (dd, 1H, J=2.7, 8.7 Hz), 7.59 (d, 1H, J=2.4 Hz), 7.43 (d, 1H, J=8.7 Hz), 7.33-7.28 (m, 2H), 6.99 (t, 1H, J=73.2 Hz), 4.24 (t, 2H, J=6.0 Hz), 3.75-3.72 (m, 2H), 3.01-2.94 (m, 2H), 2.27 (br, 1H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-2)
  3. waitmobile phase, CH3CN:H2O=5:95 increasing to CH3CN:H2O=30:42 within 12 min
  4. customThis resulted in 57.7 mg (37%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(pyridin-3-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid

Sources & evidence

ORD record
ord-17d71ad1fde04e8fa7bff07ac3356672
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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