Hydrochloric Acid → HCID 136340013, compound

HRID 1159889Notes

Reaction equation

HRID 1159889 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=4[F:32])[CH:20]=[CH:21][CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.CN(C=O)C.[NH:39]1[C:43]2[CH:44]=[CH:45][C:46]([NH2:48])=[CH:47][C:42]=2[N:41]=[N:40]1.Cl>CCO>[NH:39]1[C:43]2[CH:44]=[CH:45][C:46]([NH:48][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]6[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=6[F:32])[CH:20]=[CH:21][CH:22]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)=[CH:47][C:42]=2[N:41]=[N:40]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamideHCID 178507366HCID 178507366, compound

Product 1

HCID 136340013HCID 136340013, compoundYield 74.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a slurry of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (103 mg, 0.223 mmol.) in 1 mL of EtOH/0.5 mL of DMF, 1H-1,2,3-benzotriazol-5-amine (32 mg, 0.245 mmol) and 5 μL of conc. HCl, the reaction contents were heated to 80° C. After heating for 18 h, the reaction mixture was cooled to rt and partitioned between DCM and sat. aq. NaHCO3. The layers were separated, extracted the aqueous layer with DCM (2×10 mL), the organic layers were pooled, dried over MgSO4, filtered, reduced in vacuo. Addition of TFA, followed by titration with Et2O afforded the desired product as a yellow solid 93 mg, 63% yield. 1H NMR (400 MHz, d6-DMSO): δ 10.91 (s, 1H); 9.91 (s, 1H); 8.54 (d, J=7 Hz, 1H); 8.52-8.49 (m, 2H); 8.31 (d, J=5 Hz, 1H); 7.99 (s, 1H); 7.82 (t, J1=10 Hz, 2H); 7.60-7.53 (m, 2H); 7.50-7.45 (m, 2H); 7.37 (d, J=8 Hz, 1H); 7.23 (t, J=9 Hz, 2H); 7.13 (t, J=7 Hz, 1H); 6.55 (d, J=5 Hz, 1H). HRMS calculated C30H20F2N9O [M+H]+ 560.1759, found 560.1763.

Workup

  1. temperatureAfter heating for 18 h
  2. temperaturethe reaction mixture was cooled to rt
  3. custompartitioned between DCM and sat. aq. NaHCO3
  4. customThe layers were separated
  5. extractionextracted the aqueous layer with DCM (2×10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. additionAddition of TFA

Sources & evidence

ORD record
ord-18bddbf8a8344e54afa93e86b5255cfa
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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