Sodium Carbonate → 5-{6-[(3S)-3-Methylmorpholin-4-yl]-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine

HRID 421435Notes

Reaction equation

HRID 421435 reaction equation
O1CCOCC1.Cl[C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][N:14]2[CH2:17][C:18]([F:21])([F:20])[F:19])=[C:10]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]2[CH3:28])[N:9]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[N:39][C:40]([NH2:43])=[N:41][CH:42]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH3:28][C@H:23]1[CH2:24][O:25][CH2:26][CH2:27][N:22]1[C:10]1[N:9]=[C:8]([C:37]2[CH:38]=[N:39][C:40]([NH2:43])=[N:41][CH:42]=2)[N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH2:17][C:18]([F:21])([F:20])[F:19]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 593335792-Chloro-6-[(3S)-3-methylmorpholin-4-yl]-9-(2,2,2-trifluoroethyl)-9H-purine

Product 1

HCID 593336465-{6-[(3S)-3-Methylmorpholin-4-yl]-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amineYield 99.3%

Reagents, catalysts & solvents 2

HCID 178420534HCID 178420534, compoundCatalystHCID 962WaterSolvent2×

Procedure

Tetrakis triphenylphosphine (62 mg, 0.05 mmol) was added to a dioxane (5 ml)-water (1 ml) suspension of 2-chloro-6-[(3S)-3-methylmorpholin-4-yl]-9-(2,2,2-trifluoroethyl)-9H-purine (361 mg, 1.08 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (261 mg, 1.18 mmol), and sodium carbonate (342 mg, 3.23 mmol). The reaction mixture was heated to reflux for 2.5 hours and returned to room temperature. Water was added to the reaction mixture and the resulting mixture was extracted with 10% methanol-chloroform. The organic layer was dried over anhydrous magnesium sulfate and, after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform to chloroform:methanol=15:1) to give a solid. The resulting solid was washed with 50% ethyl acetate-hexane and dried to give the title compound (423 mg) as a powder.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2.5 hours
  3. customreturned to room temperature
  4. extractionthe resulting mixture was extracted with 10% methanol-chloroform
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationafter filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (chloroform to chloroform:methanol=15:1)
  9. customto give a solid
  10. washThe resulting solid was washed with 50% ethyl acetate-hexane
  11. customdried

Sources & evidence

ORD record
ord-7ed0f71cc5d64df59d250b02bc603144
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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