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

HRID 1478168Notes

Reaction equation

HRID 1478168 reaction equation
[CH:1]([O:4][CH:5]1[CH2:10][CH2:9][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]([OH:18])=O)[C:12]=2[CH3:19])=[CH:7][CH2:6]1)([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:44][C:45]1[C:46](=[O:58])[N:47]([CH:52]2[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]2)[N:48]([CH3:51])[C:49]=1[CH3:50].C(N(CC)CC)C>CN1C(=O)CCC1>[CH:52]1([N:47]2[C:46](=[O:58])[C:45]([NH:44][C:16]([C:13]3[C:12]([CH3:19])=[C:11]([C:8]4[CH2:9][CH2:10][CH:5]([O:4][CH:1]([CH3:2])[CH3:3])[CH2:6][CH:7]=4)[O:15][N:14]=3)=[O:18])=[C:49]([CH3:50])[N:48]2[CH3:51])[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57]1

Participants

6

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 1185110625-(4-Isopropoxycyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid

Product 1

HCID 118511096N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(4-isopropoxycyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 5-(4-isopropoxycyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid (174 mg, 0.656 mmol) in dry NMP (3 mL), HATU (274 mg, 0.721 mmol) was added followed by 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (151 mg, 0.721 mmol) and triethylamine (0.201 mL, 1.443 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 (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was dissolved in DMSO and purified using a UV-directed reverse phase chromatography with a gradient of 40-80% MeCN in water (0.1% formic acid) over 9.5 minutes. The product fraction was added to EtOAc (50 mL) and washed with a saturated aqueous NaHCO3 solution (50 mL). The organic phase was 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 (30 mL), brine (30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe crude material was dissolved in DMSO
  7. custompurified
  8. customover 9.5 minutes
  9. additionThe product fraction was added to EtOAc (50 mL)
  10. washwashed with a saturated aqueous NaHCO3 solution (50 mL)
  11. dry with materialThe organic phase was dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e56e7a432b074b4cafd26c9799b76a9b
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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