Dimethylformamide → N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(4-isopropylcyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxamide

HRID 1478149Notes

Reaction equation

HRID 1478149 reaction equation
[CH:1]([CH:4]1[CH2:9][CH2:8][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]([OH:17])=O)[C:11]=2[CH3:18])=[CH:6][CH2:5]1)([CH3:3])[CH3:2].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:30][C:31]1[C:32](=[O:44])[N:33]([CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[N:34]([CH3:37])[C:35]=1[CH3:36].C(N(CC)CC)C>C(Cl)Cl.CS(C)=O.O>[CH:38]1([N:33]2[C:32](=[O:44])[C:31]([NH:30][C:15]([C:12]3[C:11]([CH3:18])=[C:10]([C:7]4[CH2:8][CH2:9][CH:4]([CH:1]([CH3:2])[CH3:3])[CH2:5][CH:6]=4)[O:14][N:13]=3)=[O:17])=[C:35]([CH3:36])[N:34]2[CH3:37])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 612730214-amino-2-cyclohexyl-1,5-dimethyl-2,3-dihydro-1H-pyrazol-3-one2×HCID 1185110505-(4-Isopropylcyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid

Product 1

HCID 118511061N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(4-isopropylcyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxamide

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of [5-(4-isopropylcyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid] (42 mg, 0.168 mmol) in dry DCM (3 mL) under nitrogen was added DMF (0.026 mL, 0.337 mmol) followed by oxalyl chloride (0.016 mL, 0.185 mmol) and the mixture was stirred at room temperature for 30 mins. 4-Amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (38.8 mg, 0.185 mmol) was added followed by triethylamine (0.070 mL, 0.505 mmol) and the mixture was stirred for 30 mins. Water was added and the mixture was stirred vigorously before passing through a phase separating cartridge. The organic eluent was collected and concentrated under reduced pressure to give an orange oil. The crude material was dissolved in DMSO (0.9 mL) and purified using mass-directed automated reverse phase chromatography over a 9.5 minute gradient of 50-98% MeCN in water (0.1% formic acid). The product fraction was concentrated under reduced pressure. The remaining aqueous was treated with a saturated aqueous solution of sodium hydrogen carbonate and extracted with DCM, passing the organic extracts through a phase separating cartridge. The solvent was removed under a stream of air and dried under reduced pressure to afford the title compound;

Workup

  1. stirringthe mixture was stirred for 30 mins
  2. stirringthe mixture was stirred vigorously
  3. customseparating cartridge
  4. customThe organic eluent was collected
  5. concentrationconcentrated under reduced pressure
  6. customto give an orange oil
  7. custompurified
  8. customover a 9.5 minute
  9. concentrationThe product fraction was concentrated under reduced pressure
  10. additionThe remaining aqueous was treated with a saturated aqueous solution of sodium hydrogen carbonate
  11. extractionextracted with DCM
  12. customseparating cartridge
  13. customThe solvent was removed under a stream of air
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-70fbb9a8d82f449a8d2b6eeb90ca02e0
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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