N-甲基吡咯烷酮 → 5-{9-Isobutyl-8-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

HRID 421355

反应方程式

HRID 421355 反应方程式
[NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CN1CCCC1=O.Cl[C:16]1[N:17]([CH2:38][CH:39]([CH3:41])[CH3:40])[C:18]2[C:23]([N:24]=1)=[C:22]([N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[N:21]=[C:20]([C:31]1[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=1)[N:19]=2.[S:42](Cl)([CH3:45])(=[O:44])=[O:43]>C(N(CC)CC)C>[CH2:38]([N:17]1[C:16]([N:1]2[CH2:7][CH2:6][CH2:5][N:4]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:3][CH2:2]2)=[N:24][C:23]2[C:18]1=[N:19][C:20]([C:31]1[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=1)=[N:21][C:22]=2[N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[CH:39]([CH3:41])[CH3:40]

参与物

6

反应物 4

HCID 13387N-甲基吡咯烷酮HCID 31297甲基磺酰氯HCID 68163高哌嗪HCID 593335495-(8-Chloro-9-isobutyl-6-morpholino-9H-purin-2-yl)pyrimidin-2-amine

产物 1

HCID 593336605-{9-Isobutyl-8-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine收率 110.9%

试剂、催化剂与溶剂 1

HCID 8471三乙胺溶剂

反应条件

温度
120 °C

实验过程

Homopiperazine (130 mg, 1.3 mmol) and N-methylpyrrolidone (1 ml) were added to 5-(8-chloro-9-isobutyl-6-morpholin-4-yl-9H-purin-2-yl)pyrimidin-2-amine (100 mg, 0.26 mmol) and the resulting mixture stirred at 120° C. for 2 hours. The reaction mixture was cooled and partitioned with methylene chloride and water, the organic layer was dried over magnesium sulfate, and the solvent was concentrated under reduced pressure. Triethylamine (110 μl) and mesyl chloride (45 μl, 0.58 mmol) were added to the resulting mixture and the resulting mixture was stirred for 0.5 hours. The reaction mixture was partitioned with ethyl acetate and water and the organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid) to give the title compound (153 mg, 75%) as a white solid.

后处理

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned with methylene chloride and water
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. concentrationthe solvent was concentrated under reduced pressure
  5. stirringthe resulting mixture was stirred for 0.5 hours
  6. customThe reaction mixture was partitioned with ethyl acetate and water
  7. dry with materialthe organic layer was dried over magnesium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid)

来源与证据

ORD记录
ord-42295b25c6bb4432a476fc87dcd0cd31
来源数据集
uspto-grants-2012_01
专利号
US08097622B2

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