3-Fluoroaniline → 2,2,2-Trifluoro-N-[3-(3-{2-[(3-fluorophenyl)amino]-4-pyrimidinyl}pyrazolo-[1,5-a]pyridin-2-yl)phenyl]acetamide

HRID 1159883Notes

Reaction equation

HRID 1159883 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:29])[C:25]([F:28])([F:27])[F:26])[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.[F:30][C:31]1[CH:32]=[C:33]([CH:35]=[CH:36][CH:37]=1)[NH2:34]>C(O)C.Cl>[F:26][C:25]([F:28])([F:27])[C:24]([NH:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:34][C:33]4[CH:35]=[CH:36][CH:37]=[C:31]([F:30])[CH:32]=4)[N:7]=3)=[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]3[N:10]=2)[CH:18]=1)=[O:29]

Participants

5

Reactant 2

HCID 97423-FluoroanilineHCID 59513717N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide

Product 1

HCID 595138292,2,2-Trifluoro-N-[3-(3-{2-[(3-fluorophenyl)amino]-4-pyrimidinyl}pyrazolo-[1,5-a]pyridin-2-yl)phenyl]acetamide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide (2.27 g, 5.4 mmol) in ethanol (60 mL) was added 3-fluoroaniline (0.62 mL, 6.48 mmol) and 5 drops of conc. HCl. The reaction was heated to 80° C. for 16 h, allowed to cool to rt and concentrated. The mixture was partioned between DCM and saturated aq. NaHCO3. The separated aqueous layer was extracted with DCM (2×) and the combined organic layers were dried over MgSO4, filtered and concentrated to give, after trituration of the residue, the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 9.78 (s, 1H), 8.83 (d, 1H, J=7.2), 8.43 (d, 1H, J=9.2), 8.30 (d, 1H, J=5.2), 7.97 (s, 1H), 7.79-7.72 ((m, 2H), 7.52-7.40 (m, 4H), 7.22 (q, 1H, J=7.6), 7.12 (t, 1H, J=6.8), 6.69 (m, 1H), 6.56 (d, 1H, J=5.2).

Workup

  1. temperatureto cool to rt
  2. concentrationconcentrated
  3. extractionThe separated aqueous layer was extracted with DCM (2×)
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give

Sources & evidence

ORD record
ord-33a13c0752d0428e88158c66d181b78a
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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