Methanol → HCID 178485584, compound

HRID 1948043Notes

Reaction equation

HRID 1948043 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) δ 1.37-1.57 (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-9116511a31514cf6a3410e3837858b83
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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