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

HRID 1876620ノート

反応式

HRID 1876620 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178420534HCID 178420534、化合物触媒HCID 962Water溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-55a6c76e89eb430393841f35789209bf
出典データセット
uspto-grants-2012_11
特許番号
US08309546B2

反応ノート

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