Aniline → 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(phenylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoate

HRID 1396987Notes

Reaction equation

HRID 1396987 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:8]([N:10]2[CH:14]([C:15](O)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.CN1CCOCC1.[NH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>C(#N)C>[CH:1]1([CH2:6][C@@H:7]([C:8](=[O:9])[N:10]2[CH:14]([C:15]([NH:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)[CH2:18][C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6115AnilineHCID 79724-MethylmorpholineHCID 27340604-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-iumHCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

Product 1

HCID 682880441,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(phenylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoateYield 90%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (352 mg, 1.0 mmol) in acetonitrile (10 mL) at 0° C. was added 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium (656 mg, 2.0 mmol) and N-methylmorpholine (0.29 mL, 2.6 mmol). The reaction was stirred for 2 hours at 0° C. Aniline (93 mg, 1.0 mmol) was added to the reaction, which was allowed to warm to room temperature and stirred for 3 hours. The solvent was then removed under reduced pressure, and water (5 mL) and DCM (15 mL) were added to the residue. The phases were separated. The aqueous phase was extracted twice with DCM (15 mL), and the combined organics were dried over sodium sulfate and concentrated. The resulting residue was purified by Combiflash silica gel chromatography (0-60% EtOAc in hex) to give 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-oxo-4-{5-[(phenylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoate (386 mg, 0.90 mmol, 90% yield) as a yellow oil. MS: 428 ([M+H]).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 3 hours
  3. customThe solvent was then removed under reduced pressure, and water (5 mL) and DCM (15 mL)
  4. additionwere added to the residue
  5. customThe phases were separated
  6. extractionThe aqueous phase was extracted twice with DCM (15 mL)
  7. dry with materialthe combined organics were dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe resulting residue was purified by Combiflash silica gel chromatography (0-60% EtOAc in hex)

Sources & evidence

ORD record
ord-d65b45e0a1f345978b4c7de374c54ce1
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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