Diisopropylethylamine → HCID 178428266, compound

HRID 452862Notes

Reaction equation

HRID 452862 reaction equation
[NH2:1][C@H:2]1[C@H:6]([CH3:7])[CH2:5][N:4]([C:8]2[N:13]=[C:12]([NH:14][C:15]3[CH:19]=[CH:18][NH:17][N:16]=3)[CH:11]=[C:10]([CH3:20])[N:9]=2)[CH2:3]1.[C:21](=O)([O:32][C@@H:33]([CH3:38])[C:34]([F:37])([F:36])[F:35])[O:22]C1C=CC([N+]([O-])=O)=CC=1.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[F:35][C:34]([F:37])([F:36])[C@@H:33]([O:32][C:21](=[O:22])[NH:1][C@@H:2]1[C@H:6]([CH3:7])[CH2:5][N:4]([C:8]2[N:9]=[C:10]([CH3:20])[CH:11]=[C:12]([NH:14][C:15]3[CH:19]=[CH:18][NH:17][N:16]=3)[N:13]=2)[CH2:3]1)[CH3:38]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 687562104-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonateHCID 178428265HCID 178428265, compound

Product 1

HCID 178428266HCID 178428266, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 2-[(3S,4R)-3-amino-4-methylpyrrolidin-1-yl]-6-methyl-N-(1H-pyrazol-3-yl)pyrimidin-4-amine (20 mg) in CHCl3 (10 ml) was added 4-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonate (41 mg) prepared in Step 1 of Example 1 and DIEA (19 mg) at room temperature. After 4-hour stirring at 60° C., the resulting mixture was cooled to room temperature and concentrated. The residue was diluted with MeOH (5 mL). To the resulting mixture was added potassium carbonate (100 mg) at 0° C. and stirred at 0° C. for 30 min. The mixture was poured into saturated aqueous solution of NH4Cl and extracted with CHCl3. The extract was washed with brine, dried over MgSO4 and concentrated. The residue was purified with silica gel column chromatography (eluent: CHCl3/MeOH=99/1˜80/20) to give (2S)-1,1,1-trifluoropropan-2-yl{(3R,4R)-4-methyl-1-[4-methyl-6-(1H-pyrazol-3-ylamino)pyrimidin-2-yl]pyrrolidin-3-yl}carbamate as a pale yellow foam.

Workup

  1. temperaturethe resulting mixture was cooled to room temperature
  2. concentrationconcentrated
  3. additionThe residue was diluted with MeOH (5 mL)
  4. additionTo the resulting mixture was added potassium carbonate (100 mg) at 0° C.
  5. stirringstirred at 0° C. for 30 min
  6. additionThe mixture was poured into saturated aqueous solution of NH4Cl
  7. extractionextracted with CHCl3
  8. washThe extract was washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe residue was purified with silica gel column chromatography (eluent: CHCl3/MeOH=99/1˜80/20)

Sources & evidence

ORD record
ord-a942c14c84d04f05876bf57f1020ff88
Source dataset
uspto-grants-2013_07
Patent number
US08492397B2

Reaction notes

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