Triethylamine → N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-5-(spiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxamide

HRID 1478154Notes

Reaction equation

HRID 1478154 reaction equation
[CH3:1][C:2]1[C:3]([C:17](O)=[O:18])=[N:4][O:5][C:6]=1[C:7]1[CH2:16][CH2:15][C:10]2([CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:9][CH:8]=1.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.CS(C)=O>[CH:52]1([N:47]2[C:46](=[O:58])[C:45]([NH:44][C:17]([C:3]3[C:2]([CH3:1])=[C:6]([C:7]4[CH2:16][CH2:15][C:10]5([CH2:11][CH2:12][CH2:13][CH2:14]5)[CH2:9][CH:8]=4)[O:5][N:4]=3)=[O:18])=[C:49]([CH3:50])[N:48]2[CH3:51])[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57]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 1185110464-Methyl-5-(spiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxylic acid

Product 1

HCID 118511184N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-5-(spiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxamide

Reagents, catalysts & solvents 2

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

Procedure

To a stirred solution of 4-methyl-5-(spiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxylic acid (95 mg, 0.364 mmol) in dry NMP (3 ml), HATU (152 mg, 0.400 mmol) was added followed by 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (84 mg, 0.400 mmol) and triethylamine (0.111 mL, 0.800 mmol) and this was stirred at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc (30 mL) and 1M NaOH (aq) (30 mL) and the organic phase was washed with water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give an orange oil. The crude material was dissolved in DMSO and purified using UV-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 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 reaction mixture was partitioned between EtOAc (30 mL) and 1M NaOH (aq) (30 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. customto give an orange oil
  7. custompurified
  8. customover a 9.5 minute
  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 extracts were dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b8b9c7fe86fb4c66bbe47e9a23ecebf8
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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