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

HRID 1478177Notes

Reaction equation

HRID 1478177 reaction equation
[CH3:1][C:2]([CH3:15])([CH3:14])/[CH:3]=[CH:4]/[C:5]1[O:9][N:8]=[C:7]([C:10]([OH:12])=O)[C:6]=1[CH3:13].[NH2:16][C:17]1[C:18](=[O:30])[N:19]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[N:20]([CH3:23])[C:21]=1[CH3:22].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:24]1([N:19]2[C:18](=[O:30])[C:17]([NH:16][C:10]([C:7]3[C:6]([CH3:13])=[C:5](/[CH:4]=[CH:3]/[C:2]([CH3:1])([CH3:15])[CH3:14])[O:9][N:8]=3)=[O:12])=[C:21]([CH3:22])[N:20]2[CH3:23])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]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 118511138(E)-5-(3,3-Dimethylbut-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid

Product 1

HCID 118511123(E)-N-(2-Cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-(3,3-dimethylbut-1-en-1-yl)-4-methylisoxazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(E)-5-(3,3-Dimethylbut-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid (102 mg, 0.487 mmol) and 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (112 mg, 0.536 mmol) in DMF (2 mL) were treated with DIPEA (0.341 mL, 1.950 mmol) and HATU (222 mg, 0.585 mmol). The reaction mixture was stirred at room temperature for 2 hours. The resulting mixture was treated with water and extracted with EtOAc. The combined organic extracts were washed with 0.5 M LiCl (aq), dried over MgSO4, filtered and the solvent was removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-100% EtOAc in iso-hexane afforded the title compound;

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic extracts were washed with 0.5 M LiCl (aq)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe crude material was adsorbed onto silica and purification by chromatography
  7. washeluting with 0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-84b6b854ae29480ca29148a0c34c48a4
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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