Sodium Methoxide → N-[(1R,3S)-3-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]cyclohexyl]-morpholine-4-carboxamide

HRID 526989Notes

Reaction equation

HRID 526989 reaction equation
[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@@H:31]([NH:35][C:36]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[O:37])[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+]>CO>[F:1][C:2]1[C:3]([NH:28][C@H:29]2[CH2:34][CH2:33][CH2:32][C@@H:31]([NH:35][C:36]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[O:37])[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

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 68007840HCID 68007840, compound2×

Product 1

HCID 68007473N-[(1R,3S)-3-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]cyclohexyl]-morpholine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

N-[(1R,3S)-3-[[5-fluoro-2-[5-fluoro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-4-yl]amino]cyclohexyl]morpholine-4-carboxamide, 44f, (2.0 g, 3.2 mmol) was suspended in methanol (50 mL) and treated with 25% sodium methoxide in methanol (19.9 mL, 92.3 mmol). After stirring for 1 hour, the solvent was evaporated under reduced pressure, and the residue was partitioned between water (100 mL) and ethyl acetate (100 mL). The organic layer was collected, dried on Na2SO4 and concentrated to provide the crude product as a yellow solid. This material was purified by silica gel chromatography on a 40 g column, using DCM/MeOH 1-6%. The purified fractions were treated with 2N HCl in ether and concentrated to provide 1.5 g of N-[(1R,3S)-3-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]cyclohexyl]-morpholine-4-carboxamide as a white solid.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customthe residue was partitioned between water (100 mL) and ethyl acetate (100 mL)
  3. customThe organic layer was collected
  4. customdried on Na2SO4
  5. concentrationconcentrated
  6. customto provide the crude product as a yellow solid
  7. customThis material was purified by silica gel chromatography on a 40 g column
  8. additionThe purified fractions were treated with 2N HCl in ether
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-1dd32134051d40dc90c77e7b96f612f2
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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