Sodium Bicarbonate → HCID 67070321, compound

HRID 2390873Notes

Reaction equation

HRID 2390873 reaction equation
[NH2:1][C:2]1[CH:36]=[CH:35][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]3[C:16]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:17][CH:18]=[CH:19][CH:20]=3)[CH:12]=[C:11]([C:29]([CH3:32])([CH3:31])[CH3:30])[C:10]=2[O:33][CH3:34])=[O:7])=[CH:4][C:3]=1[F:37].O.[F:39][C:40]([F:44])([F:43])[CH:41]=O.C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O.O.CCOC(C)=O>[CH2:22]([O:21][C:16]1[C:15]([C:13]2[CH:12]=[C:11]([C:29]([CH3:31])([CH3:32])[CH3:30])[C:10]([O:33][CH3:34])=[C:9]([NH:8][C:6](=[O:7])[C:5]3[CH:35]=[CH:36][C:2]([NH:1][CH2:41][C:40]([F:44])([F:43])[F:39])=[C:3]([F:37])[CH:4]=3)[CH:14]=2)=[CH:20][CH:19]=[CH:18][N:17]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 27813662,2,2-Trifluoroacetaldehyde hydrateHCID 5003444Sodium cyanoborohydrideHCID 67070070HCID 67070070, compound

Product 1

HCID 67070321HCID 67070321, compoundYield 38.1%

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 962WaterSolventHCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Procedure

step 3—To a solution of 318 (201 mg, 0.402 mmol) in TFA (4 mL) at RT was added trifluoroacetaldehyde hydrate (98 mg, 0.845 mmol) and H2O (2 drops). The reaction mixture was stirred at RT for 5 min, and then sodium cyanoborohydride (33 mg, 0.523 mmol) was added. Gas evolution was briefly observed. The reaction mixture was stirred at RT for 4.5 h, then diluted with H2O and EtOAc and carefully poured into sat'd NaHCO3. The layers were separated, and the organic phase was subsequently twice washed sequentially with sat'd. NaHCO3, H2O and brine. The organic layer was dried (MgSO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography, eluting with an EtOAc/hexane gradient (0% to 30% EtOAc) to afford 89 mg (38%) of N-[5-(2-benzyloxy-pyridin-3-yl)-3-tert-butyl-2-methoxy-phenyl]-3-fluoro-4-(2,2,2-trifluoro-ethylamino)-benzamide (320) as a foamy, light yellow solid.

Workup

  1. stirringThe reaction mixture was stirred at RT for 4.5 h
  2. customThe layers were separated
  3. washthe organic phase was subsequently twice washed sequentially with sat'd
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by SiO2 chromatography
  8. washeluting with an EtOAc/hexane gradient (0% to 30% EtOAc)

Sources & evidence

ORD record
ord-92313386c63641efbb79d35836e6d04b
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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