Triethylamine → HCID 118511055, compound

HRID 1478199Notes

Reaction equation

HRID 1478199 reaction equation
Br[CH:2]1[CH:7]([CH3:8])[CH2:6][O:5][CH:4]([C:9]2[O:13][N:12]=[C:11]([C:14]([O-:16])=O)[C:10]=2[CH3:17])[CH2:3]1.[K+].CC1C(C([O-])=O)=NOC=1C1CC=C(C)CO1.[K+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:60][C:61]1[C:62](=[O:74])[N:63]([CH:68]2[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]2)[N:64]([CH3:67])[C:65]=1[CH3:66].C(N(CC)CC)C>CN1C(=O)CCC1>[CH:68]1([N:63]2[C:62](=[O:74])[C:61]([NH:60][C:14]([C:11]3[C:10]([CH3:17])=[C:9]([CH:4]4[CH2:3][CH:2]=[C:7]([CH3:8])[CH2:6][O:5]4)[O:13][N:12]=3)=[O:16])=[C:65]([CH3:66])[N:64]2[CH3:67])[CH2:69][CH2:70][CH2:71][CH2:72][CH2:73]1

Participants

7

Reactant 5

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 118511044HCID 118511044, compoundHCID 118511144HCID 118511144, compound

Product 1

HCID 118511055HCID 118511055, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of potassium 5-(4-bromo-5-methyltetrahydro-2H-pyran-2-yl)-4-methylisoxazole-3-carboxylate and potassium 4-methyl-5-(5-methyl-3,6-dihydro-2H-pyran-2-yl)isoxazole-3-carboxylate (crude mixture) (217 mg, 0.634 mmol) in dry NMP (4 mL) was added HATU (Fluorochem) (265 mg, 0.697 mmol), 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (133 mg, 0.634 mmol) and triethylamine (0.194 mL, 1.395 mmol). The reaction mixture was stirred at room temperature overnight and partitioned between EtOAc (25 mL) and 1M NaOH (25 mL). The organics were washed with water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was dissolved in DMSO and purified using UV-directed automated reverse phase chromatography over a 9.5 minute gradient of 30-70% MeCN in water (0.1% formic acid). The product fractions were added to EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (50 mL). The organic layers were dried over MgSO4, filtered and the solvent removed under reduced pressure to afford the title compounds.

Workup

  1. custompartitioned between EtOAc (25 mL) and 1M NaOH (25 mL)
  2. washThe organics were washed with water (30 mL), brine (30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe crude material was dissolved in DMSO
  7. custompurified
  8. customover a 9.5 minute
  9. additionThe product fractions were added to EtOAc (50 mL)
  10. washwashed with saturated aqueous NaHCO3 (50 mL)
  11. dry with materialThe organic layers were dried over MgSO4
  12. filtrationfiltered
  13. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-1c176a4e30554bb0a0f217e9c69a64bc
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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