Acetic Acid → 3-amino-N-methyl-6-(4-oxocyclohexyl)pyridine-2-carboxamide

HRID 511476Notes

Reaction equation

HRID 511476 reaction equation
[NH2:1][C:2]1[C:3]([C:18]([NH:20][CH3:21])=[O:19])=[N:4][C:5]([CH:8]2[CH2:17][CH2:16][C:11]3(OCC[O:12]3)[CH2:10][CH2:9]2)=[CH:6][CH:7]=1.CC(O)=O.O>>[NH2:1][C:2]1[C:3]([C:18]([NH:20][CH3:21])=[O:19])=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11](=[O:12])[CH2:16][CH2:17]2)=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 672562083-Amino-6-(1,4-dioxaspiro[4.5]dec-8-yl)-N-methylpyridine-2-carboxamide2×

Product 1

HCID 672552993-amino-N-methyl-6-(4-oxocyclohexyl)pyridine-2-carboxamide

Conditions

Temperature
75 °C

Procedure

A mixture of 3-Amino-6-(1,4-dioxaspiro[4.5]dec-8-yl)-N-methylpyridine-2-carboxamide (Compound 232C, 0.160 g, 0.549 mmol) in AcOH (1.0 mL, 18 mmol) and H2O (0.2 mL, 10 mmol) was warmed to 75° C. for 2.5 hours, after which, the reaction was cooled and concentrated in vacuo. The residue was taken up in water and basified with a saturated aqueous solution of K2CO3. This mixture was extracted three times with DCM and the combined organic layers were dried over Na2SO4, filtered and concentrated to a brown tar. This was taken up in DCM, treated with silica and concentrated and loaded into a sample cartridge. The product was isolated after purification on an ISCO Combiflash unit (eluting with 0-4% MeOH/DCM) as 53 mg of a white crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ1.97-2.13 (m, 4H), 2.26 (dt, J=14.40, 2.02 Hz, 2H), 2.52-2.59 (m, 2H), 2.77 (d, J=5.05 Hz, 3H), 3.05 (tdd, J=11.43, 3.79, 3.66 Hz, 1H), 6.65 (s, 2H), 7.09 (d, J=8.30 Hz, 1H), 7.20 (d, J=8.30 Hz, 1H), 8.42 (d, J=4.80 Hz, 1H). MS (ES+): m/z=247.87 (90) [M+1]. HPLC: tR=2.95 min (ZQ3, polar—5 min).

Workup

  1. temperatureafter which, the reaction was cooled
  2. concentrationconcentrated in vacuo
  3. extractionThis mixture was extracted three times with DCM
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a brown tar
  7. additiontreated with silica
  8. concentrationconcentrated
  9. customThe product was isolated
  10. customafter purification
  11. washon an ISCO Combiflash unit (eluting with 0-4% MeOH/DCM) as 53 mg of a white crystalline solid
  12. custom5 min

Sources & evidence

ORD record
ord-124ffebec67f4b7da8a09c0293e3f880
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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