Sodium Carbonate → 5-[9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-2-yl]-N-methylpyrimidin-2-amine

HRID 1876508Notes

Reaction equation

HRID 1876508 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.Cl[C:14]1[N:22]=[C:21]2[C:17]([N:18]=[CH:19][N:20]2[CH2:23][CH:24]2[CH2:26][CH2:25]2)=[C:16]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[N:15]=1.[CH3:33][NH:34][C:35]1[N:40]=[CH:39][C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][N:36]=1>C(OCC)(=O)C.O>[CH:24]1([CH2:23][N:20]2[CH:19]=[N:18][C:17]3[C:21]2=[N:22][C:14]([C:38]2[CH:37]=[N:36][C:35]([NH:34][CH3:33])=[N:40][CH:39]=2)=[N:15][C:16]=3[N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 467396412-Methylaminopyrimidine-5-boronic acid, pinacol esterHCID 593335522-chloro-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purine

Product 1

HCID 593336695-[9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purin-2-yl]-N-methylpyrimidin-2-amineYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium carbonate (2.40 g, 22.7 mmol) and tetrakis triphenylphosphine palladium (0.44 g, 0.38 mmol) were added to a 1,4-dioxane (44.0 ml)-water (22.0 ml) mixture solution of 2-chloro-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purine (2.22 g, 7.56 mmol) and 2-methylaminopyrimidine-5-boronic acid pinacol ester (2.31 g, 9.82 mmol) at room temperature and the resulting mixture was heated to reflux for 3.5 hours in an argon atmosphere. The reaction mixture was left standing to cool and then poured into water and ethyl acetate was added to separate the layers. The solid precipitated in the aqueous layer was collected by filtration, washed with water, and then dried at 50° C. under reduced pressure. Meanwhile, the organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, then the filtrate was concentrated under reduced pressure, and the resulting solid was washed with dichloromethane and collected by filtration. These solids were combined to give the title compound (1.68 g, 61%) as a white solid.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 3.5 hours in an argon atmosphere
  3. waitThe reaction mixture was left
  4. temperatureto cool
  5. additionwas added
  6. customto separate the layers
  7. customThe solid precipitated in the aqueous layer
  8. filtrationwas collected by filtration
  9. washwashed with water
  10. customdried at 50° C. under reduced pressure
  11. dry with materialMeanwhile, the organic layer was dried over anhydrous sodium sulfate
  12. filtrationthe mixture was filtrated
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. washthe resulting solid was washed with dichloromethane
  15. filtrationcollected by filtration

Sources & evidence

ORD record
ord-067a5c28dc634432b80dd7711539ca5d
Source dataset
uspto-grants-2012_11
Patent number
US08309546B2

Reaction notes

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