Ethyl Acetate → (S)-(1-(2-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-3,3-dimethylbutyl)-1H-1,2,3-triazol-4-yl)methanol

HRID 1055152Notes

Reaction equation

HRID 1055152 reaction equation
[F:1][C:2]1[C:3]([NH:28][C@@H:29]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:30][N:31]2[CH:35]=[C:34]([CH2:36][OH:37])[N:33]=[N:32]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)=[N:6][CH:7]=1.C[O-].[Na+].[NH4+].[Cl-].CCOC(C)=O>C1COCC1>[F:1][C:2]1[C:3]([NH:28][C@@H:29]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:30][N:31]2[CH:35]=[C:34]([CH2:36][OH:37])[N:33]=[N:32]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 71251336(S)-(1-(2-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-3,3-dimethylbutyl)-1H-1,2,3-triazol-4-yl)methanol2×

Product 1

HCID 71251329(S)-(1-(2-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-3,3-dimethylbutyl)-1H-1,2,3-triazol-4-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-(1-(2-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-3,3-dimethylbutyl)-1H-1,2,3-triazol-4-yl)methanol, 218a, (0.11 g, 0.19 mmol) in THF (5 mL) was added NaOMe (0.17 mL of 25% solution in MeOH, 0.75 mmol). After stirring the reaction mixture at room temperature for 30 minutes, the mixture was diluted into aqueous saturated NH4Cl solution (5 mL) and EtOAc (10 mL). The organic layer was separated, dried (MgSO4), filtered concentrated in vacuo. The crude product was purified by silica gel chromatography (0-10% MeOH/CH2Cl2) to afford 41 mg of the desired product as an off-white solid: 1H NMR (400 MHz, CD3OD) δ 8.51 (d, J=8.0 Hz, 1H), 8.16 (s, 1H), 8.09 (s, 1H), 7.93 (d, J=3.5 Hz, 1H), 7.38 (s, 1H), 5.08 (m, 1H), 5.00-4.90 (m, 1H), 4.74 (s, 2H), 4.60 (m, 1H), 1.2 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=1.90 minutes (M+H) 429.26.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography (0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-995314d692f344af82d6d69c3325a1bf
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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