Diisopropylethylamine → HCID 178428263, compound

HRID 2383507Notes

Reaction equation

HRID 2383507 reaction equation
[O:1]1[CH2:6][CH2:5][NH:4][C@@H:3]2[CH2:7][N:8]([C:10]3[N:15]=[C:14]([NH:16][C:17]4[CH:21]=[CH:20][NH:19][N:18]=4)[CH:13]=[C:12]([CH3:22])[N:11]=3)[CH2:9][C@@H:2]12.[C:23](=O)([O:34][C@@H:35]([CH3:40])[C:36]([F:39])([F:38])[F:37])[O:24]C1C=CC([N+]([O-])=O)=CC=1.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[CH3:22][C:12]1[CH:13]=[C:14]([NH:16][C:17]2[CH:21]=[CH:20][NH:19][N:18]=2)[N:15]=[C:10]([N:8]2[CH2:7][C@@H:3]3[C@H:2]([O:1][CH2:6][CH2:5][N:4]3[C:23]([O:34][C@@H:35]([CH3:40])[C:36]([F:39])([F:38])[F:37])=[O:24])[CH2:9]2)[N:11]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 687562104-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonateHCID 178428264HCID 178428264, compound

Product 1

HCID 178428263HCID 178428263, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-[(4aR,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl]-6-methyl-N-(1H-pyrazol-3-yl)pyrimidin-4-amine (20 mg) in CHCl3 (3 mL) were added 4-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonate (37 mg) prepared in Referential Example 2 and DIEA (30 mg) at room temperature. After 4-hour stirring at 100° C. in a sealed tube, 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 (4aR,7aR)-6-[4-methyl-6-(1H-pyrazol-3-ylamino)pyrimidin-2-yl]hexahydropyrrolo[3,4-b][1,4]oxazine-4(4aH)-carboxylate 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-67861d74f01d467db992f8bc8393d901
Source dataset
uspto-grants-2012_09
Patent number
US08263632B2

Reaction notes

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