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

HRID 421435노트

반응식

HRID 421435 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178420534HCID 178420534, 화합물촉매HCID 962Water용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7ed0f71cc5d64df59d250b02bc603144
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08097622B2

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