Ethyl Acetate → 2-((1S,3S)-3-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-1-hydroxycyclohexyl)ethanenitrile

HRID 75038Notes

Reaction equation

HRID 75038 reaction equation
[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@:31]([CH2:36][C:37]#[N:38])([OH:35])[CH2:30]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+].CCOC(C)=O>CO.[Cl-].[Na+].O>[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@:31]([CH2:36][C:37]#[N:38])([OH:35])[CH2:30]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 3

HCID 8857Ethyl AcetateHCID 10942334Sodium MethoxideHCID 680083052-((1S,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-1-hydroxycyclohexyl)ethanenitrile2×

Product 1

HCID 680073442-((1S,3S)-3-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-1-hydroxycyclohexyl)ethanenitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 2-((1S,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-1-hydroxycyclohexyl)ethanenitrile, 69b, (0.14 g, 0.26 mmol) in methanol (10 mL) was added sodium methoxide (0.06 g, 0.26 mmol). After stirring at room temperature for 2 minutes, the reaction mixture was diluted into EtOAc and brine. The separated organic phase was dried over MgSO4, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (10% MeOH/CH2Cl2) to afford 46 mg of desired product: 1H NMR (300.0 MHz, MeOD) δ 8.65 (dd, J=2.8, 9.6 Hz, 1H), 8.19 (s, 1H), 8.14 (dd, J=2.0, 2.5 Hz, 1H), 7.98 (d, J=4.1 Hz, 1H), 4.66 (dd, J=8.0, 15.8 Hz, 1H), 2.64 (s, 2H), 2.20 (d, J=12.6 Hz, 2H), 2.01 (dd, J=3.4, 9.8 Hz, 2H), 1.84-1.75 (m, 1H), 1.63-1.47 (m, 2H), 1.33 (dd, J=3.6, 12.4 Hz, 1H) ppm; LCMS RT=2.31 (M+H) 385.45.

Workup

  1. dry with materialThe separated organic phase was dried over MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by silica gel chromatography (10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-92a8466189834370b389cdecb4813d72
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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