Hydrochloric Acid → HCID 59513721, compound

HRID 1159890Notes

Reaction equation

HRID 1159890 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.[CH3:34][N:35]([CH:37]=[O:38])C.[NH2:39][C:40]1[CH:41]=C(CC(N)=O)[CH:43]=[CH:44][CH:45]=1.Cl.[CH3:51]CO>>[C:37]([NH:35][C:34]1[CH:41]=[C:40]([NH:39][C:2]2[N:7]=[C:6]([C:8]3[C:9]([C:17]4[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]5[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=5[F:32])[CH:20]=[CH:21][CH:22]=4)=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)[CH:45]=[CH:44][CH:43]=1)(=[O:38])[CH3:51]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 6228DimethylformamideHCID 1088232-(3-aminophenyl)acetamideHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Product 1

HCID 59513721HCID 59513721, compoundYield 26%

Conditions

Temperature
70 °C

Procedure

To a slurry of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (133 mg, 0.288 mmol.) in 1 mL of EtOH/0.25 mL of DMF, N/(3-aminophenyl)acetamide (71 mg, 0.32 mmol.) and 5 uL of conc. HCl, the reaction contents were heated to 70° C. After heating for 18 h, the reaction was cooled to rt, partitioned the reaction with EtOAc and sat. aq. NaHCO3. The layers were separated, extracted the aqueous layer with EtOAc (2×10 mL), the organic layers were pooled, dried over MgSO4, filtered, reduced in vacuo onto silica. Purification via ISCO (hexanes:EtOAc) to afforded a white solid, 43 mg (26% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.92 (s, 1H); 9.81 (s, 1H); 9.52 (s, 1H); 8.81 (d, J=7 Hz, 1H); 8.54 (d, J=9 Hz, 1H); 8.21 (d, J=6, 1H); 7.94 (d, J=16 Hz, 2H); 7.81 (d, J=9 Hz, 1H); 7.58-7.54 (m, 1H); 7.47-7.41 (m, 2H); 7.34 (t, J=10 Hz, 2H); 7.25-7.09 (m, 5H): 6.47 (d, J=5 Hz, 1H); 5.72 (s, 1H); 1.99 (s, 3H). HRMS calculated C32H24F2N7O2 [M+H]+ 576.1960, found 576.1945.

Workup

  1. temperatureAfter heating for 18 h
  2. temperaturethe reaction was cooled to rt
  3. custompartitioned
  4. customthe reaction with EtOAc and sat. aq. NaHCO3
  5. customThe layers were separated
  6. extractionextracted the aqueous layer with EtOAc (2×10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customPurification via ISCO (hexanes:EtOAc)
  10. customto afforded a white solid, 43 mg (26% yield)

Sources & evidence

ORD record
ord-442bc44dd20146dea53093de89b0cdf3
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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