Sodium Methoxide → HCID 68007337, compound

HRID 527099Notes

Reaction equation

HRID 527099 reaction equation
[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([NH:9][CH:10]2[CH2:15][CH:14]([CH3:16])[CH2:13][CH:12]([NH:17][C:18]3[C:23]([F:24])=[CH:22][N:21]=[C:20]([C:25]4[C:33]5[C:28](=[N:29][CH:30]=[C:31]([F:34])[CH:32]=5)[N:27](S(C5C=CC(C)=CC=5)(=O)=O)[CH:26]=4)[N:19]=3)[CH2:11]2)=[O:8])[CH2:3]1.C[O-].[Na+]>CO>[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([NH:9][C@@H:10]2[CH2:15][C@H:14]([CH3:16])[CH2:13][C@H:12]([NH:17][C:18]3[C:23]([F:24])=[CH:22][N:21]=[C:20]([C:25]4[C:33]5[C:28](=[N:29][CH:30]=[C:31]([F:34])[CH:32]=5)[NH:27][CH:26]=4)[N:19]=3)[CH2:11]2)=[O:8])[CH2:3]1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 68008307(3S)-3-fluoro-N-(3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-5-methylcyclohexyl)pyrrolidine-1-carboxamide2×

Product 1

HCID 68007337HCID 68007337, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of (3S)-3-fluoro-N-(3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-5-methylcyclohexyl)pyrrolidine-1-carboxamide, 76d, (0.090 g, 0.143 mmol) in MeOH (2.5 ml) was added 25% sodium methoxide in methanol (2 ml). The reaction was stirred at room temperature for 30 minutes and quenched with aqueous saturated NH4Cl. The methanol was removed in-vacuo and the residue was extracted with EtOAc and water. The organics were dried over sodium sulfate and concentrated to dryness. The resulting crude racemate was purified by SFC separation on a chiral column. The second peak was concentrated in vacuo to afford 32 mg of enantiomerically pure (S)-3-fluoro-N-((1R,3S,5R)-3-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-5-methylcyclohexyl)pyrrolidine-1-carboxamide as a white solid: LCMS RT=1.89 (M+1) 474.2, (M−1) 472.4; SFC RT=3.2 min., 15% MeOH @ 5 mL/min on an ODH (4.6*100), 100 bar, 35 C, 220 nm; 1H NMR (300 MHz, DMSO) δ 12.26 (s, 1H), 8.41 (dd, J=9.9, 2.8 Hz, 1H), 8.32-8.18 (m, 2H), 8.14 (d, J=4.0 Hz, 1H), 7.53 (d, J=7.6 Hz, 1H), 6.02 (d, J=7.9 Hz, 1H), 5.28 (d, J=53.6 Hz, 1H), 4.35-4.00 (m, 1H), 3.81-3.09 (m, 12H), 2.24-1.77 (m, J=41.2, 26.1, 10.6 Hz, 4H), 1.74-1.51 (m, 1H), 1.51-1.22 (m, 1H), 1.14-0.70 (m, 4H).

Workup

  1. customquenched with aqueous saturated NH4Cl
  2. customThe methanol was removed in-vacuo
  3. extractionthe residue was extracted with EtOAc and water
  4. dry with materialThe organics were dried over sodium sulfate
  5. concentrationconcentrated to dryness
  6. customThe resulting crude racemate was purified by SFC separation on a chiral column
  7. concentrationThe second peak was concentrated in vacuo

Sources & evidence

ORD record
ord-dca1fd6091884798a84c3df4fa1e70a7
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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