Sodium Bicarbonate → HCID 71247954, compound

HRID 1055136Notes

Reaction equation

HRID 1055136 reaction equation
[F:1][C:2]([F:40])([F:39])[CH:3]([OH:38])[CH2:4][C@@H:5]([NH:10][C:11]1[C:16]([F:17])=[CH:15][N:14]=[C:13]([C:18]2[C:26]3[C:21](=[N:22][CH:23]=[C:24]([F:27])[CH:25]=3)[N:20](S(C3C=CC(C)=CC=3)(=O)=O)[CH:19]=2)[N:12]=1)[C:6]([CH3:9])([CH3:8])[CH3:7].C[O-].[Na+].C([O-])(O)=O.[Na+]>CCOC(C)=O>[F:40][C:2]([F:1])([F:39])[CH:3]([OH:38])[CH2:4][C@@H:5]([NH:10][C:11]1[C:16]([F:17])=[CH:15][N:14]=[C:13]([C:18]2[C:26]3[C:21](=[N:22][CH:23]=[C:24]([F:27])[CH:25]=3)[NH:20][CH:19]=2)[N:12]=1)[C:6]([CH3:7])([CH3:8])[CH3:9]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 10942334Sodium MethoxideHCID 86714782HCID 86714782, compound2×

Product 1

HCID 71247954HCID 71247954, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4R)-1,1,1-trifluoro-4-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-5,5-dimethylhexan-2-ol, 182a, (0.053 g, 0.091 mmol) was added NaOMe (0.019 g of 25% solution in MeOH, 0.091 mmol). The reaction mixture was stirred at room temperature for 5 minutes. The reaction mixture was diluted into EtOAc and aqueous saturated NaHCO3 solution. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes) to afford 26 mg of the desired product, 66: 1H NMR (400 MHz, CDCl3) δ 9.40 (s, 1H), 8.47 (dd, J=9.3, 2.7 Hz, 1H), 8.15 (s, 1H), 8.10 (d, J=2.7 Hz, 1H), 7.99 (d, J=2.8 Hz, 1H), 5.54 (s, 1H), 4.84 (d, J=7.5 Hz, 1H), 4.23 (t, J=9.9 Hz, 1H), 3.91 (s, 1H), 2.07-1.97 (m, 1H), 1.62 (t, J=13.0 Hz, 1H), 1.01 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=2.42 minutes (M+H) 430.44.

Workup

  1. dry with materialThe organic phase was dried over MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe crude residue was purified by silica gel chromatography (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-e965d11a199646f9b879f78994de9b05
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

Loading…