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

HRID 1478163Notes

Reaction equation

HRID 1478163 reaction equation
[CH3:1][C:2]1[C:3]([C:17]([OH:19])=O)=[N:4][O:5][C:6]=1[C:7]1[CH2:16][CH2:15][C:10]2([CH2:14][O:13][CH2:12][CH2:11]2)[CH2:9][CH:8]=1.[NH2:20][C:21]1[C:22](=[O:34])[N:23]([CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[N:24]([CH3:27])[C:25]=1[CH3:26].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:28]1([N:23]2[C:22](=[O:34])[C:21]([NH:20][C:17]([C:3]3[C:2]([CH3:1])=[C:6]([C:7]4[CH2:16][CH2:15][C:10]5([CH2:14][O:13][CH2:12][CH2:11]5)[CH2:9][CH:8]=4)[O:5][N:4]=3)=[O:19])=[C:25]([CH3:26])[N:24]2[CH3:27])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 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 1185111014-Methyl-5-(2-oxaspiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxylic acid

Product 1

HCID 118511075N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-5-(2-oxaspiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of [4-methyl-5-(2-oxaspiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxylic acid] (40 mg, 0.152 mmol) in DMF (3 mL) was treated with 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (38.2 mg, 0.182 mmol), DIPEA (0.106 mL, 0.608 mmol) and HATU (75 mg, 0.198 mmol). The resulting mixture was stirred at room temperature for 16 hours. Water was added to the mixture and the aqueous was extracted with EtOAc (×2). The combined organic extracts were washed with 0.5M lithium chloride (aq), dried over MgSO4, filtered and the solvent removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-5% MeOH in EtOAc afforded the title compound;

Workup

  1. extractionthe aqueous was extracted with EtOAc (×2)
  2. washThe combined organic extracts were washed with 0.5M lithium chloride (aq)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe crude material was adsorbed onto silica and purification by chromatography
  7. washeluting with 0-5% MeOH in EtOAc

Sources & evidence

ORD record
ord-b3c85bc92a924ddb84419dd92149a2c3
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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