Triethylamine → US10195181, Example 25a

HRID 1478203Notes

Reaction equation

HRID 1478203 reaction equation
[C:1]([CH:5]1[CH2:9][O:8][CH:7]([C:10]2[O:14][N:13]=[C:12]([C:15]([O-:17])=O)[C:11]=2[CH3:18])[O:6]1)([CH3:4])([CH3:3])[CH3:2].[K+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH2:51][C:52]1[C:53](=[O:65])[N:54]([CH:59]2[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]2)[N:55]([CH3:58])[C:56]=1[CH3:57]>CN1C(=O)CCC1.CCOC(C)=O.O>[C:1]([CH:5]1[CH2:9][O:8][CH:7]([C:10]2[O:14][N:13]=[C:12]([C:15]([NH:51][C:52]3[C:53](=[O:65])[N:54]([CH:59]4[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64]4)[N:55]([CH3:58])[C:56]=3[CH3:57])=[O:17])[C:11]=2[CH3:18])[O:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

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 118511106HCID 118511106, compound

Product 1

HCID 118511076US10195181, Example 25a

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of potassium 5-(4-(tert-butyl)-1,3-dioxolan-2-yl)-4-methylisoxazole-3-carboxylate (43.5 mg, 0.148 mmol) in NMP (0.7 mL) was added HATU (62.0 mg, 0.163 mmol), triethylamine (45.5 μl, 0.326 mmol) and 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (31.0 mg, 0.148 mmol) and the reaction mixture was stirred at room temperature overnight. To the resulting mixture was added water and EtOAc. The organics were washed with brine (×2), dried over MgSO4, filtered and the solvent removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-100% EtOAc in iso-hexane afforded the title compound as a mixture of diastereoisomers.

Workup

  1. washThe organics were washed with brine (×2)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure
  5. customThe crude material was adsorbed onto silica and purification by chromatography
  6. washeluting with 0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-f51da8b4363c4845a6c90ae25a65b3d4
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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