Methanol → HCID 178485584, compound

HRID 511475Notes

Reaction equation

HRID 511475 reaction equation
[NH2:1][C:2]1[C:3]([C:15]([NH:17][CH3:18])=[O:16])=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1.CO.[BH4-].[Na+]>>[NH2:1][C:2]1[C:3]([C:15]([NH:17][CH3:18])=[O:16])=[N:4][C:5]([C@H:8]2[CH2:9][CH2:10][C@H:11]([OH:14])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 672552993-amino-N-methyl-6-(4-oxocyclohexyl)pyridine-2-carboxamide2×

Product 1

HCID 178485584HCID 178485584, compound

Conditions

Temperature
0 °C

Procedure

A solution of 3-amino-N-methyl-6-(4-oxocyclohexyl)pyridine-2-carboxamide (Compound 232B, 53 mg, 0.21 mmol) in MeOH (3 mL, 70 mmol) was cooled to 0° C. and treated with sodium borohydride (8.1 mg, 0.21 mmol). The mixture was stirred at 0° C. for 20 minutes. The reaction was quenched with sat. aq. NH4Cl (1 mL) and concentrated. The residue was taken up in 1 mL H2O and EtOAc (30 m). The layers were separated. The aqueous layer was saturated with salt and washed again with ˜20 mL of EtOAc. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude solid was taken up in DCM, treated with silica and concentrated. This silica was loaded into a sample column and purified on an ISCO Combiflash unit (0-7% MeOH/DCM) to isolate the product as a mixture of predominantly trans isomer. 1H NMR (400 MHz, CHLOROFORM-d) δ1.37-1.57 (m, 4H), 1.92-2.01 (m, 2H), 2.07-2.16 (m, 2H), 2.55 (tt, J=11.87, 3.54 Hz, 1H), 2.99 (d, J=5.05 Hz, 3H), 3.63-3.77 (m, 1H), 5.81 (br. s., 2H), 6.95 (d, J=8.40 Hz, 1H), 7.04 (d, J=8.40 Hz, 1H), 8.11 (br. s., 1H).

Workup

  1. customThe reaction was quenched with sat. aq. NH4Cl (1 mL)
  2. concentrationconcentrated
  3. customThe layers were separated
  4. washwashed again with ˜20 mL of EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additiontreated with silica
  10. concentrationconcentrated
  11. custompurified on an ISCO Combiflash unit (0-7% MeOH/DCM)
  12. customto isolate the product
  13. additionas a mixture of predominantly trans isomer

Sources & evidence

ORD record
ord-82d35662a09143af87ae79389369befe
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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