4-Methylmorpholine → 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate

HRID 1396991Notes

Reaction equation

HRID 1396991 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.[CH3:50][CH:51]([C:53]1[N:58]=[C:57]([NH2:59])[CH:56]=[CH:55][CH:54]=1)C>C(#N)C>[CH:1]1([CH2:6][C@@H:7]([C:8]([N:10]2[CH:14]([C:15]([NH:59][C:57]3[CH:56]=[CH:55][CH:54]=[C:53]([CH2:51][CH3:50])[N:58]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:18][C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27340604-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-iumHCID 217255966-(Propan-2-yl)pyridin-2-amineHCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

Product 1

HCID 682879751,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoateYield 81%

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., and then 6-(1-methylethyl)-2-pyridinamine (177 mg, 1.30 mmol) was added to the reaction. The mixture was allowed to warm to room temperature and was stirred for 3 hours. The solvent was removed under reduced pressure, and then water (5 mL) and DCM (15 mL) were added. 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 (0-100% EtOAc in hex) to give 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate (368 mg, 0.81 mmol, 81% yield) as a yellow oil. MS: 457 ([M+H]+).

Workup

  1. temperatureto warm to room temperature
  2. stirringwas stirred for 3 hours
  3. customThe solvent was removed under reduced pressure
  4. additionwater (5 mL) and DCM (15 mL) were added
  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 (0-100% EtOAc in hex)

Sources & evidence

ORD record
ord-59f32b5a5a56416d8c5e1eb92842f2d7
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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