Triethylamine → HCID 118511029, compound

HRID 1478184Notes

Reaction equation

HRID 1478184 reaction equation
[CH3:1][C:2]1[C:3]([C:17]([OH:19])=O)=[N:4][O:5][C:6]=1[CH:7]1[CH2:16][CH2:15][C:10]2([O:14][CH2:13][CH2:12][O:11]2)[CH2:9][CH2:8]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]([CH:7]4[CH2:8][CH2:9][C:10]5([O:11][CH2:12][CH2:13][O:14]5)[CH2:15][CH2:16]4)[O:5][N:4]=3)=[O:19])=[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 118511134HCID 118511134, compound

Product 1

HCID 118511029HCID 118511029, compound

Reagents, catalysts & solvents 2

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

Procedure

To a stirred solution of 4-methyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)isoxazole-3-carboxylic acid (239 mg, 0.894 mmol) in dry NMP (3 mL), HATU (374 mg, 0.984 mmol) was added followed by 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (206 mg, 0.984 mmol) and triethylamine (0.274 mL, 1.967 mmol). The mixture was stirred at room temperature for 16 hours. The resulting mixture was partitioned between EtOAc (20 mL) and 1M NaOH (20 mL). 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 adsorbed onto silica and purification by chromatography eluting with 0-2% MeOH in DCM afforded crude material. Isolated material was dissolved in DMSO (2 mL) and triturated with water (30 mL). The resulting suspension was filtered under reduced pressure and the solid was washed with water (20 mL) and allowed to dry under vacuum to afford the title compound;

Workup

  1. customThe resulting mixture was partitioned between EtOAc (20 mL) and 1M NaOH (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. customThe crude material was adsorbed onto silica and purification by chromatography
  7. washeluting with 0-2% MeOH in DCM
  8. customafforded crude material
  9. customtriturated with water (30 mL)
  10. filtrationThe resulting suspension was filtered under reduced pressure
  11. washthe solid was washed with water (20 mL)
  12. customto dry under vacuum

Sources & evidence

ORD record
ord-6f5c62a93ca742ab8c7e8d37bc766109
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

Loading…