N-methyl-2-pyrrolidone → 5-{9-Isobutyl-8-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

HRID 1876545

反応式

HRID 1876545 の反応式
[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]

参加物

6

反応物 4

HCID 13387N-methyl-2-pyrrolidoneHCID 31297Methanesulfonyl chlorideHCID 68163Hexahydro-1,4-diazepineHCID 593335495-(8-Chloro-9-isobutyl-6-morpholino-9H-purin-2-yl)pyrimidin-2-amine

生成物 1

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

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-cbaf247855bd48caaa18cfafd32bf9ec
出典データセット
uspto-grants-2012_11
特許番号
US08309546B2

関連ノート

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