Triethylamine → Smurf1-IN-1

HRID 1478800Notes

Reaction equation

HRID 1478800 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[N:11]1[C:15]([CH3:16])=[C:14]([C:17]([OH:19])=O)[N:13]=[N:12]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].C(N(CC)CC)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:9][CH2:10]2)[CH:5]=[CH:4][C:3]=1[N:11]1[C:15]([CH3:16])=[C:14]([C:17]([NH:20][C:21]2[C:22](=[O:34])[N:23]([CH:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[N:24]([CH3:27])[C:25]=2[CH3:26])=[O:19])[N:13]=[N:12]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 612730214-amino-2-cyclohexyl-1,5-dimethyl-2,3-dihydro-1H-pyrazol-3-one2×HCID 1185132751-(2-chloro-4-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid

Product 1

HCID 118513267Smurf1-IN-1

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

1-(2-Chloro-4-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid (15 g, 54.0 mmol) and 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate A)(11.30 g, 54.0 mmol) were slurried in EtOAc (150 mL). The reaction mixture was cooled to 10° C. and triethylamine (18.82 mL, 135 mmol) was added dropwise, followed by dropwise addition of T3P (50% w/w in EtOAc) (47.7 mL, 81 mmol) over 15 mins, maintaining a temperature <10° C. The reaction mixture was allowed to warm to RT and stirred for 2.5 hrs. The resulting mixture was quenched with sat. sodium bicarbonate (aq) (150 ml). The layers were separated and the organic layer was washed with sat. sodium bicarbonate (aq) (50 ml), water (150 ml) and brine (150 ml). The organic extracts were dried over MgSO4 and charcoal. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The crude material was slurried in ethyl acetate (335 ml) and heated to reflux with stirring. The hot mixture was filtered and the filtrate was seeded and at left to stand at room temperature overnight. The resulting crystalline solid was collected by filtration and dried under reduced pressure at 40° C. over 2 days to yield the title compound.

Workup

  1. temperaturemaintaining a temperature <10° C
  2. temperatureto warm to RT
  3. customThe resulting mixture was quenched with sat. sodium bicarbonate (aq) (150 ml)
  4. customThe layers were separated
  5. washthe organic layer was washed with sat. sodium bicarbonate (aq) (50 ml), water (150 ml) and brine (150 ml)
  6. dry with materialThe organic extracts were dried over MgSO4 and charcoal
  7. filtrationThe desiccant was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. temperatureheated
  10. temperatureto reflux
  11. stirringwith stirring
  12. filtrationThe hot mixture was filtered
  13. waitat left
  14. waitto stand at room temperature overnight
  15. filtrationThe resulting crystalline solid was collected by filtration
  16. customdried under reduced pressure at 40° C. over 2 days

Sources & evidence

ORD record
ord-4c6cd19e77ff4942b72be023c4c303a1
Source dataset
uspto-grants-2016_08
Patent number
US09403833B2

Reaction notes

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