N-methyl-2-pyrrolidone → Ds-7423

HRID 421366Notes

Reaction equation

HRID 421366 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.Cl[C:9]1[N:10]([CH2:31][C:32]([F:35])([F:34])[F:33])[C:11]2[C:16]([N:17]=1)=[C:15]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[N:14]=[C:13]([C:24]1[CH:25]=[N:26][C:27]([NH2:30])=[N:28][CH:29]=1)[N:12]=2.CN1CC[CH2:39][C:38]1=[O:42]>>[C:38]([N:3]1[CH2:4][CH2:5][N:6]([C:9]2[N:10]([CH2:31][C:32]([F:35])([F:34])[F:33])[C:11]3[C:16]([N:17]=2)=[C:15]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:14]=[C:13]([C:24]2[CH:25]=[N:26][C:27]([NH2:30])=[N:28][CH:29]=2)[N:12]=3)[CH2:7][C@H:2]1[CH3:1])(=[O:42])[CH3:39]

Participants

4

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 73304342-Methylpiperazine, (R)-HCID 593335342-(2-aminopyrimidin-5-yl)-8-chloro-6-(morpholin-4-yl)-9-(2,2,2-trifluoroethyl)-9H-purine

Product 1

HCID 45378170Ds-7423Yield 52%

Conditions

Temperature
100 °C

Procedure

(2R)-2-Methylpiperazine (241 mg, 2.41 mmol) and N-methyl-2-pyrrolidone (2 ml) were added to 5-[8-chloro-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (200 mg, 0.48 mmol) and the resulting mixture was stirred at 100° C. for 2 hours. The reaction mixture was partitioned with chloroform and water, the organic layer was dried over magnesium sulfate, and the solvent was concentrated under reduced pressure. Acetic anhydride (68 μl) and triethylamine (200 μl) were added to the residue with ice cooling and the resulting mixture was stirred for 1 hour and partitioned with ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was dried over magnesium sulfate, then the solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (chloroform:methanol=20:1) to give the title compound (127 mg, 52%) as a colorless solid.

Workup

  1. customThe reaction mixture was partitioned with chloroform and water
  2. dry with materialthe organic layer was dried over magnesium sulfate
  3. concentrationthe solvent was concentrated under reduced pressure
  4. additionAcetic anhydride (68 μl) and triethylamine (200 μl) were added to the residue with ice cooling
  5. stirringthe resulting mixture was stirred for 1 hour
  6. custompartitioned with ethyl acetate and saturated aqueous sodium bicarbonate solution
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel chromatography (chloroform:methanol=20:1)

Sources & evidence

ORD record
ord-dd998a3696d74b44a4a87ce40382ccee
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

Loading…