Cesium carbonate → ethyl 3-(2-chloro-6-morpholino-9H-purin-9-yl)propanoate

HRID 334131Notes

Reaction equation

HRID 334131 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>CN(C=O)C.[Cl-].[Na+].O.C(Cl)Cl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:4]([N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[N:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonate2×HCID 68320Ethyl 3-bromopropionate2×HCID 32746034-(2-chloro-9H-purin-6-yl)morpholine

Product 1

HCID 86667344ethyl 3-(2-chloro-6-morpholino-9H-purin-9-yl)propanoateYield 83%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 4-(2-chloro-9H-purin-6-yl)morpholine (3.0 g, 13 mmol) in DMF (39 mL) was treated with cesium carbonate (8.2 g, 25 mmol) and stirred at ambient temperature for 10 minutes. 3-bromopropanoic acid, ethyl ester (6.8 g, 38 mmol) was introduced and the reaction mixture was heated at 50° C. for 2 hr. Partial conversion prompted the addition of cesium carbonate (8.2 g, 25 mmol) and 3-bromopropanoic acid, ethyl ester (6.8 g, 38 mmol), and the reaction mixture was heated at 70° C. The reaction mixture was cooled to ambient temperature and diluted with brine and DCM and the layers separated. The aqueous phase was extracted into DCM (3×), dried over sodium sulfate, filtered, and absorbed onto celite for purification by flash chromatography to afford ethyl 3-(2-chloro-6-morpholino-9H-purin-9-yl)propanoate as a white solid (3.5 g, 83%). LC/MS (ESI+): m/z 340 (M+H)

Workup

  1. temperaturethe reaction mixture was heated at 50° C. for 2 hr
  2. temperaturethe reaction mixture was heated at 70° C
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. customthe layers separated
  5. extractionThe aqueous phase was extracted into DCM (3×)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customabsorbed onto celite for purification by flash chromatography

Sources & evidence

ORD record
ord-fa819d2d285f4a938745121d95e5182d
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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