Cesium carbonate → methyl 2-(2-chloro-8-(2-hydroxypropan-2-yl)-6-morpholino-9H-purin-9-yl)propanoate

HRID 334135Notes

Reaction equation

HRID 334135 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:11]([OH:14])([CH3:13])[CH3:12])[NH:8]2)=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH:28]([CH3:33])[C:29]([O:31][CH3:32])=[O:30]>CN(C=O)C.O.C(OCC)(=O)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([C:11]([OH:14])([CH3:13])[CH3:12])[N:8]2[CH:28]([CH3:33])[C:29]([O:31][CH3:32])=[O:30])=[C:4]([N:15]2[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)[N:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonate2×HCID 95576Methyl 2-bromopropionate2×HCID 178458928HCID 178458928, compound

Product 1

HCID 86667354methyl 2-(2-chloro-8-(2-hydroxypropan-2-yl)-6-morpholino-9H-purin-9-yl)propanoateYield 27.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

2-(2-chloro-6-morpholino-9H-purin-8-yl)propan-2-ol (4.6 g, 15 mmol) was dissolved in DMF (16 mL), treated with cesium carbonate (10 g, 31 mmol) and methyl 2-bromopropanoate (7.6 g, 46 mmol), and heated at 50° C. for 3 hr. Partial conversion prompted addition of cesium carbonate (10 g, 31 mmol) and methyl 2-bromopropanoate (7.6 g, 46 mmol) and the reaction mixture was heated at 50° C. for 20 hr. The reaction mixture was cooled to ambient temperature and diluted with water and ethyl acetate and the layers separated. The aqueous phase was extracted into ethyl acetate (3×), dried over sodium sulfate, filtered, and absorbed onto celite for purification by flash chromatography to afford methyl 2-(2-chloro-8-(2-hydroxypropan-2-yl)-6-morpholino-9H-purin-9-yl)propanoate as a yellow foam (1.6 g, 26%). LC/MS (ESI+): m/z 384 (M+H)

Workup

  1. temperaturethe reaction mixture was heated at 50° C. for 20 hr
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. customthe layers separated
  4. extractionThe aqueous phase was extracted into ethyl acetate (3×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customabsorbed onto celite for purification by flash chromatography

Sources & evidence

ORD record
ord-0c08b3e9d54b48609cfe3d27611a76ec
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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