Water → HCID 86710247, compound

HRID 2405941Notes

Reaction equation

HRID 2405941 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:11]=[N:12][N:13]([CH2:15][CH2:16][C@@:17]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[C:18](O)=[O:19])[CH:14]=1.CN1CCOCC1.[O:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH:34]1[O:39][NH2:40].O>CC1OCCC1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:11]=[N:12][N:13]([CH2:15][CH2:16][C@@:17]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[C:18]([NH:40][O:39][CH:34]2[CH2:35][CH2:36][CH2:37][CH2:38][O:33]2)=[O:19])[CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 79724-MethylmorpholineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70817543HCID 70817543, compound

Product 1

HCID 86710247HCID 86710247, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a solution of (2R)-4-[4-(1,3-benzoxazol-2-yl)-1H-pyrazol-1-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (0.420 g, 1.16 mmol) in 2-MeTHF (30 mL) was added N-methyl morpholine (0.165 g, 1.62 mmol, 1.4 eq), followed by CDMT (0.244 g, 1.39 mmol, 1.2 eq). The reaction mixture was allowed to stir for one hour. O-tetrahydro-2H-pyran-2-yl-hydroxylamine (0.162 g, 1.39 mmol, 1.2 eq) was added, and the reaction 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 30%-100% ethyl acetate/heptane to yield (2R)-4-[4-(1,3-benzoxazol-2-yl)-1H-pyrazol-1-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (410 mg, 77% yield) as a colorless oil. LC-MS M−H 461.3.

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 30%-100% ethyl acetate/heptane

Sources & evidence

ORD record
ord-1ce9dfce222240b38ef01cc961f53f39
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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