Ethyl Acetate → (S)-4-(2-chloro-9-methyl-9H-purin-6-yl)-3-methylmorpholine

HRID 2063361Notes

Reaction equation

HRID 2063361 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4](Cl)[N:3]=1.[CH3:13][C@H:14]1[CH2:19][O:18][CH2:17][CH2:16][NH:15]1.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>C(O)C.CN(C=O)C.C(OCC)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([N:15]2[CH2:16][CH2:17][O:18][CH2:19][C@@H:14]2[CH3:13])[N:3]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 17125532,6-dichloro-9-methyl-9H-purineHCID 12012220(3S)-3-methylmorpholine

Product 1

HCID 58222544(S)-4-(2-chloro-9-methyl-9H-purin-6-yl)-3-methylmorpholineYield 85.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2,6-dichloro-9-methyl-9H-purine (1.41 g, 6.96 mmol) and (S)-3-methylmorpholine (817 mg, 8.08 mmol, 1.16 eq.) in anhydrous ethanol (60 mL) and anhydrous DMF (5.0 mL) was added N,N-diisopropylethylamine (1.8 mL, 10.43 mmol, 1.5 eq.), and the reaction mixture was stirred at RT under N2 for 3 days. The reaction mixture was diluted with 1:1 v/v diethyl ether:ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution, water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 80% ethyl acetate in hexane) to give the desired compound (a-4) as a solid (1.59 g, 85.2%). 1H NMR (CDCl3, 500 MHz) δ ppm 7.65 (s, 1H), 5.34 (broad d, 2H), 3.99 (m, 1), 3.76 (m, 5H), 3.61 (ddd, 1H), 3.36 (broad s), 1H), 1.39 (d, 3H).

Workup

  1. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution, water and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 80% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e8913a2f6d604bbb84b28d207cf65046
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

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