Cesium carbonate → 2,6-Difluoro-N-{3-[3-{2-[(3-fluorophenyl)amino]-4-pyrimidinyl}-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamide

HRID 1160002Notes

Reaction equation

HRID 1160002 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=4)[N:22]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[F:83][C:84]1[CH:92]=[CH:91][CH:90]=[C:89]([F:93])[C:85]=1[C:86]([NH2:88])=[O:87]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:83][C:84]1[CH:92]=[CH:91][CH:90]=[C:89]([F:93])[C:85]=1[C:86]([NH:88][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=4)[N:22]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][N:10]3[N:9]=2)[CH:3]=1)=[O:87]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 874392,6-DifluorobenzamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 595138564-[2-(3-bromophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine

Product 1

HCID 595137942,6-Difluoro-N-{3-[3-{2-[(3-fluorophenyl)amino]-4-pyrimidinyl}-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamideYield 30%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-[2-(3-bromophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine (125 mg, 0.24 mmol) in dioxane (10 mL) was added Pd2 dba3 (7 mg, 0.007 mmol), Cs2CO3 (94 mg, 0.34 mmol), Xantphos (7 mg, 0.011 mmol), and 2,6-difluorobenzamide (44 mg, 0.28 mmol). The reaction mixture was then subjected to microwave irradiation (Personal Chemistry Optimizer, 170° C., 15 min). The reaction was then cooled and the mixture partitioned in EtOAc (100 mL) and water (25 mL). The organic layer was separated, dried (over MgSO4) and concentrated. The crude material was purified by silica gel column chromatography (20-50% EA/Hex) to provide the title compound (43 mg, 30%) as an beige solid. 1H NMR (400 MHz, d6-DMSO): δ 10.95 (s, 1H), 9.88 (s, 1H), 9.54 (s, 1H), 8.54 (d, J=9.3 Hz, 1H), 8.38 (d, J=5.3 Hz, 1H), 8.07 (s, 1H), 7.80 (d, J=8.8 Hz, 1H), 7.71 (m, 2H), 7.59 (m, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.43 (d, J=9.3 Hz, 1H), 7.35 (d, J=7.7 Hz, 1H), 7.25 (m, 3H), 6.71 (dt, J=2.3, 8.4 Hz, 1H), 6.65 (d, J=5.1 Hz, 1H) ppm. ESIMS (M+H)+=605.

Workup

  1. customThe reaction mixture was then subjected to microwave irradiation (Personal Chemistry Optimizer, 170° C., 15 min)
  2. temperatureThe reaction was then cooled
  3. customthe mixture partitioned in EtOAc (100 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (over MgSO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel column chromatography (20-50% EA/Hex)

Sources & evidence

ORD record
ord-ea89f06dc4824a3f839d0cdd4b5c5ca6
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

Loading…