Water → HCID 86710250, compound

HRID 2405948Notes

Reaction equation

HRID 2405948 reaction equation
[CH3:1][C@@:2]([S:24]([CH3:27])(=[O:26])=[O:25])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[O:20][CH:21]=[CH:22][N:23]=3)=[CH:15][CH:14]=2)[CH:10]=[N:9]1)[C:3](O)=[O:4].CN1CCOCC1.[O:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1[O:41][NH2:42].O>CC1CCCO1>[CH3:1][C@@:2]([S:24]([CH3:27])(=[O:25])=[O:26])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[O:20][CH:21]=[CH:22][N:23]=3)=[CH:15][CH:14]=2)[CH:10]=[N:9]1)[C:3]([NH:42][O:41][CH:36]1[CH2:37][CH2:38][CH2:39][CH2:40][O:35]1)=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 79724-MethylmorpholineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70818201HCID 70818201, compound

Product 1

HCID 86710250HCID 86710250, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a solution of (2R)-2-methyl-2-(methylsulfonyl)-4-{4-[4-(1,3-oxazol-2-yl)phenyl]-1H-pyrazol-1-yl}butanoic acid (0.125 g, 0.321 mmol) in 2-methyltetrahydrofuran (20 mL) was added n-methyl morpholine (0.046 g, 0.449 mmol, 1.4 eq), followed by CDMT (0.068 g, 0.385 mmol, 1.2 eq). The reaction was allowed to stir for one hour. O-Tetrahydro-2H-pyran-2-yl-hydroxylamine (0.045 g, 0.385 mmol, 1.2 eq) was added, and the reaction mixture was allowed to stir for an additional two hours. Water (20 mL) was added, and the solution was extracted with 2-MeTHF (100 mL). The aqueous layer was re-extracted with 2-MeTHF (150 mL) and the combined organic layers were washed with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography, eluting with 50%-100% ethyl acetate/heptane to yield (2R)-2-methyl-2-(methylsulfonyl)-4-{4-[4-(1,3-oxazol-2-yl)phenyl]-1H-pyrazol-1-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (31 mg, 20% yield) as a colorless oil. LC-MS M−H 487.5.

Workup

  1. stirringto stir for an additional two hours
  2. extractionthe solution was extracted with 2-MeTHF (100 mL)
  3. extractionThe aqueous layer was re-extracted with 2-MeTHF (150 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography
  9. washeluting with 50%-100% ethyl acetate/heptane

Sources & evidence

ORD record
ord-f7169e350cde4a0e8e58e9e03ad15e02
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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