Potassium Carbonate → (R)-3-[2-Cyclopropyl-7-(1,4-dimethyl-1H-indol-3-ylmethyl)-8-oxo-7,8-dihydro-purin-9-yl]-3-phenyl-propionic acid ethyl ester

HRID 2175204Notes

Reaction equation

HRID 2175204 reaction equation
[CH2:1]([O:3][C:4](=[O:26])[CH2:5][C@@H:6]([N:13]1[C:21](=[O:22])[NH:20][C:19]2[C:14]1=[N:15][C:16]([CH:23]1[CH2:25][CH2:24]1)=[N:17][CH:18]=2)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2].C([O-])([O-])=O.[K+].[K+].[I-].[CH3:34][N:35]1[C:43]2[C:38](=[C:39]([CH3:44])[CH:40]=[CH:41][CH:42]=2)[C:37]([CH2:45][N+](C)(C)C)=[CH:36]1>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:26])[CH2:5][C@@H:6]([N:13]1[C:21](=[O:22])[N:20]([CH2:45][C:37]2[C:38]3[C:43](=[CH:42][CH:41]=[CH:40][C:39]=3[CH3:44])[N:35]([CH3:34])[CH:36]=2)[C:19]2[C:14]1=[N:15][C:16]([CH:23]1[CH2:24][CH2:25]1)=[N:17][CH:18]=2)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 17836486((1,4-Dimethylindole-3-yl)methyl)trimethylammonium iodideHCID 58497396(R)-3-(2-Cyclopropyl-8-oxo-7,8-dihydro-purin-9-yl)-3-phenyl-propionic acid ethyl ester

Product 1

HCID 58497405(R)-3-[2-Cyclopropyl-7-(1,4-dimethyl-1H-indol-3-ylmethyl)-8-oxo-7,8-dihydro-purin-9-yl]-3-phenyl-propionic acid ethyl esterYield 50.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-3-(2-cyclopropyl-8-oxo-7,8-dihydro-purin-9-yl)-3-phenyl-propionic acid ethyl ester (313 mg, 0.89 mmol) in DMF (5 ml) were added K2CO3 (234 mg, 1.7 mmol) and (1,4-Dimethyl-1H-indol-3-ylmethyl)-trimethyl-ammonium iodide (275 mg, 1.27 mmol). The reaction mixture was heated to 100° C. for 4 hours. The reaction mixture was therefore diluted with ethyl acetate and washed with water (×4). The organic phase was dried over MgSO4 and concentrated. The resulting residue was purified by chromatography, eluded with 3% methanol to 10% in CH2Cl2 to afford the titled compound (231 mg, 50%). LCMS, M++1, m/z: 509.59.

Workup

  1. washwashed with water (×4)
  2. dry with materialThe organic phase was dried over MgSO4
  3. concentrationconcentrated
  4. customThe resulting residue was purified by chromatography

Sources & evidence

ORD record
ord-664bb499fb6e441d8a56fd00e36a0a92
Source dataset
uspto-grants-2015_06
Patent number
US09062056B2

Reaction notes

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