Cesium carbonate → HCID 72202359, compound

HRID 1481495Notes

Reaction equation

HRID 1481495 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[N:9][C:10]([N:13]2[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][C:15](C=O)=[N:14]2)=[CH:11][CH:12]=1)=[O:5].[C:29](=[O:32])([O-])[O-:30].[Cs+].[Cs+].FC1C=CC=C(F)[C:37]=1[C:38]([NH2:40])=O.[CH3:46]C1(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.[O:88]1[CH2:93][CH2:92]OCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:28][C:24]1[CH:25]=[CH:26][CH:27]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:17]([C:18]([F:20])([F:19])[F:21])=[CH:16][C:15]([C:38]3[CH2:37][C:93]([CH3:92])([C:29]([O:30][CH3:46])=[O:32])[O:88][N:40]=3)=[N:14]2)=[N:9][CH:8]=1)=[O:5]

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 874392,6-DifluorobenzamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90011005HCID 90011005, compound

Product 1

HCID 72202359HCID 72202359, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
130 °C

Procedure

Step-1: 2,6-Difluoro-N-(6-(3-formyl-5-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-yl) benzamide: In a sealed tube containing a dioxane (20 mL) and cesium carbonate (2.54 g, 7.81 mmol) was purged with nitrogen gas for 10 min and then 1-(5-bromopyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carbaldehyde (prepared in step-1 of the intermediate-12; 1.0 g, 3.12 mmol), 2,6-difluorobenzamide (736 mg, 4.69 mmol) and xanthphos (180 mg, 0.31 mmol) were sequentially added. The resulting mixture was thoroughly deoxygenated by purging nitrogen gas for another 15 min and then palladium (II) acetate (35 mg, 0.15 mmol) was added to the above mixture. The sealed tube was capped and stirred at 130° C. for 6 h. The reaction mixture was then cooled to room temperature and filtered through celite. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent) to afford 700 mg (56%) of the title compound as white solid. 1HNMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 8.63 (d, J=2.0 Hz, 1H), 8.60 (dd, J=2.0 & 8.0 Hz, 1H), 8.00 (brs, 1H, D2O Exchangeable), 7.93 (d, J=8.0 Hz, 1H), 7.59-7.53 (m, 1H), 7.36 (s, 1H), 7.09 (t, J=8.0 Hz, 2H); ESI-MS (m/z) 397 (MH)+

Workup

  1. customwas purged with nitrogen gas for 10 min
  2. custom1-(5-bromopyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carbaldehyde (prepared in step-1 of the intermediate-12
  3. customThe resulting mixture was thoroughly deoxygenated
  4. customby purging nitrogen gas for another 15 min
  5. customThe sealed tube was capped
  6. temperatureThe reaction mixture was then cooled to room temperature
  7. filtrationfiltered through celite
  8. customThe filtrate was rotary evaporated
  9. customthe crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent)

Sources & evidence

ORD record
ord-3437158606a94e18a5699c64b152d439
Source dataset
uspto-grants-2016_08
Patent number
US09409898B2

Reaction notes

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