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

HRID 1478157Notes

Reaction equation

HRID 1478157 reaction equation
[CH3:1][C:2]1([CH3:16])[CH2:6][C:5]([C:7]2[O:11][N:10]=[C:9]([C:12]([OH:14])=O)[C:8]=2[CH3:15])=[CH:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:41][C:42]1[C:43](=[O:55])[N:44]([CH:49]2[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]2)[N:45]([CH3:48])[C:46]=1[CH3:47].C(N(CC)CC)C>CN1C(=O)CCC1.CS(C)=O>[CH:49]1([N:44]2[C:43](=[O:55])[C:42]([NH:41][C:12]([C:9]3[C:8]([CH3:15])=[C:7]([C:5]4[CH2:6][C:2]([CH3:1])([CH3:16])[CH2:3][CH:4]=4)[O:11][N:10]=3)=[O:14])=[C:46]([CH3:47])[N:45]2[CH3:48])[CH2:50][CH2:51][CH2:52][CH2:53][CH2:54]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 612730214-amino-2-cyclohexyl-1,5-dimethyl-2,3-dihydro-1H-pyrazol-3-one2×HCID 1185110675-(4,4-Dimethylcyclopent-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid

Product 1

HCID 118511125N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(4,4-dimethylcyclopent-1-en-1-yl)-4-methylisoxazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 5-(4,4-dimethylcyclopent-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid (105 mg, 0.475 mmol) in dry NMP (3 mL), HATU (198 mg, 0.522 mmol) was added followed by 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (109 mg, 0.522 mmol) and triethylamine (0.146 mL, 1.044 mmol). The mixture was stirred at room temperature overnight. The resulting mixture was partitioned between EtOAc (20 mL) and 1M NaOH (aq) (20 mL) and the organic phase was washed with water (20 mL), brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-60% EtOAc in iso-hexane afforded crude material. The crude material was dissolved in DMSO and purified using mass-directed automated reverse phase chromatography over a 9.5 minute gradient of 40-80% MeCN in water (0.1% formic acid). The product fraction was added to EtOAc (50 mL) and washed with a saturated aqueous NaHCO3 solution (50 mL). The organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound;

Workup

  1. customThe resulting mixture was partitioned between EtOAc (20 mL) and 1M NaOH (aq) (20 mL)
  2. washthe organic phase was washed with water (20 mL), brine (20 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was adsorbed onto silica and purification by chromatography
  7. washeluting with 0-60% EtOAc in iso-hexane
  8. customafforded crude material
  9. custompurified
  10. customover a 9.5 minute
  11. additionThe product fraction was added to EtOAc (50 mL)
  12. washwashed with a saturated aqueous NaHCO3 solution (50 mL)
  13. dry with materialThe organic extracts were dried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1ec3115c868b4345a5e926a27cc5ae74
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

Loading…