Sodium borohydride → 2-hydroxy-2-{6-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-acetamide

HRID 886559Notes

Reaction equation

HRID 886559 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[N:23]=[CH:22][N:21]=[C:20]([C:24](=[O:30])[C:25]([N:27]([CH3:29])[CH3:28])=[O:26])[CH:19]=3)[CH:16]=2)[NH:11][CH:10]=1.[BH4-].[Na+]>C(O)C>[OH:30][CH:24]([C:20]1[CH:19]=[C:18]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[CH:10][NH:11][C:12]3=[N:13][CH:14]=2)[N:23]=[CH:22][N:21]=1)[C:25]([N:27]([CH3:28])[CH3:29])=[O:26]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 598250052-{6-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-2-oxo-acetamide

Product 1

HCID 598249002-hydroxy-2-{6-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-acetamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 2-{6-[3-(2-Methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-2-oxo-acetamide (25 mg, 0.062 mmole), in ethanol (0.4 mL), was cooled to 0° C. in an ice bath and sodium borohydride (7 mg, 0.186 mmole) added in one portion. The solution was removed from the cooling bath, maintained at ambient temperature for 15 min, heated to 50° C., and maintained for an additional 15 min. After cooling to ambient temperature, water (0.2 mL) was added followed by saturated ammonium chloride (0.2 mL). The reaction mixture was concentrated to remove most of the ethanol, diluted with ethyl acetate (10 mL), and the organic layer washed with saturated sodium bicarbonate (5 mL). The resulting organic layer was dried over magnesium sulfate, filtered, and concentrated. The crude product was dissolved in DMSO and purified by mass triggered reverse phase HPLC to afford pure 2-hydroxy-2-{6-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-acetamide as a white solid. (2.3 mg, 9.2%). MS: m/z 404.2 (M+H+). 1H NMR (500 MHz, DMSO-d6) δ 2.87 (s, 3H), 3.13 (s, 3H), 3.83 (s, 3H), 5.57 (d, J=8.0 Hz, 1H), 6.08 (s, J=8.5 Hz, 1H), 7.09 (t, 1H), 7.17 (d, J=8.5 Hz, 1H), 7.34 (t, 1H), 7.58 (d, J=7.5 Hz. 1H), 7.79 (s, 1H), 8.24 (s, 1H), 8.74 (s, 1H), 9.08 (s, 1H), 9.12 (s, 1H), 12.17 (s, 1H).

Workup

  1. customThe solution was removed from the cooling bath
  2. temperatureheated to 50° C.
  3. temperaturemaintained for an additional 15 min
  4. temperatureAfter cooling to ambient temperature
  5. additionwater (0.2 mL) was added
  6. concentrationThe reaction mixture was concentrated
  7. customto remove most of the ethanol
  8. additiondiluted with ethyl acetate (10 mL)
  9. washthe organic layer washed with saturated sodium bicarbonate (5 mL)
  10. dry with materialThe resulting organic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dissolutionThe crude product was dissolved in DMSO
  14. custompurified by mass triggered reverse phase HPLC

Sources & evidence

ORD record
ord-7b3acbf82c164e3d9037fd9d97a6b60c
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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