Piperazine → 5-{9-(Cyclopropylmethyl)-8-[4-(methylsulfonyl)piperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}-4-methylpyrimidin-2-amine

HRID 421309Notes

Reaction equation

HRID 421309 reaction equation
Cl[C:2]1[N:3]([CH2:25][CH:26]2[CH2:28][CH2:27]2)[C:4]2[C:9]([N:10]=1)=[C:8]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)[N:7]=[C:6]([C:17]1[C:18]([CH3:24])=[N:19][C:20]([NH2:23])=[N:21][CH:22]=1)[N:5]=2.[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(N(CC)CC)C.[S:42](Cl)([CH3:45])(=[O:44])=[O:43]>CN1CCCC1=O>[CH:26]1([CH2:25][N:3]2[C:2]([N:29]3[CH2:34][CH2:33][N:32]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:31][CH2:30]3)=[N:10][C:9]3[C:4]2=[N:5][C:6]([C:17]2[C:18]([CH3:24])=[N:19][C:20]([NH2:23])=[N:21][CH:22]=2)=[N:7][C:8]=3[N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 4837PiperazineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59333498HCID 59333498, compound

Product 1

HCID 593336455-{9-(Cyclopropylmethyl)-8-[4-(methylsulfonyl)piperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}-4-methylpyrimidin-2-amineYield 51.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

N-Methylpyrrolidone (2 ml) was added to 5-[8-chloro-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-2-yl]-4-methylpyrimidin-2-amine (200 mg, 0.50 mmol) and piperazine (430 mg, 5.0 mmol) and the resulting mixture was stirred at 120° C. for 2 hours. The reaction mixture was partitioned with ethyl acetate and water and the organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was dissolved in tetrahydrofuran (2 ml) followed by the addition of triethylamine (140 μl, 1.0 mmol) and mesyl chloride (50 μl, 0.65 mmol) and the resulting mixture was stirred for 1 hour. The reaction mixture was partitioned with ethyl acetate and water and the organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated under reduced pressure and then the residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid) to give the title compound (135 mg, 51%) as a white solid.

Workup

  1. customThe reaction mixture was partitioned with ethyl acetate and water
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (2 ml)
  6. stirringthe resulting mixture was stirred for 1 hour
  7. customThe reaction mixture was partitioned with ethyl acetate and water
  8. washthe organic layer was washed with saturated brine
  9. dry with materialdried over magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid)

Sources & evidence

ORD record
ord-7631c0d1553b4c9bb332fa29f903cb8e
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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