Water → HCID 86710249, compound

HRID 2405944Notes

Reaction equation

HRID 2405944 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:9]#[C:10][C:11]2[CH:12]=[N:13][N:14]([CH2:16][CH2:17][C@@:18]([CH3:26])([S:22]([CH3:25])(=[O:24])=[O:23])[C:19](O)=[O:20])[CH:15]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].CN1CCOCC1.[O:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH:35]1[O:40][NH2:41].O>CC1OCCC1>[C:1]([C:3]1[CH:4]=[C:5]([C:9]#[C:10][C:11]2[CH:12]=[N:13][N:14]([CH2:16][CH2:17][C@@:18]([CH3:26])([S:22]([CH3:25])(=[O:23])=[O:24])[C:19]([NH:41][O:40][CH:35]3[CH2:36][CH2:37][CH2:38][CH2:39][O:34]3)=[O:20])[CH:15]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 79724-MethylmorpholineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70817489HCID 70817489, compound

Product 1

HCID 86710249HCID 86710249, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a solution of (2R)-4-{4-[(3-cyanophenyl)ethynyl]-1H-pyrazol-1-yl}-2-methyl-2-(methylsulfonyl)butanoic acid (0.360 g, 0.969 mmol) in 2-MeTHF (30 mL) was added N-methyl morpholine (0.139 g, 1.36 mmol, 1.4 eq), followed by CDMT (0.204 g, 1.16 mmol, 1.2 eq). The reaction mixture was allowed to stir for one hour. O-Tetrahydro-2H-pyran-2-yl-hydroxylamine (0.136 g, 1.16 mmol, 1.2 eq) was added, and the reaction mixture and 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. The crude was purified by flash chromatography, eluting with 30%-100% ethyl acetate/heptane to yield (2R)-4-{4-[(3-cyanophenyl)ethynyl]-1H-pyrazol-1-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (209 mg, 46% yield) as a colorless oil. LC-MS M−H 469.3.

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
  8. customThe crude was purified by flash chromatography
  9. washeluting with 30%-100% ethyl acetate/heptane

Sources & evidence

ORD record
ord-f9f9ef3b492c4ab1be0ee0fd0a9c5353
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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