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Dimethylformamide → 3-(1-cyano-1-methylethyl)-N-{4-methyl-3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]phenyl}benzamide

HRID 1800737
ノート
印刷プレビュー

反応式

HRID 1800737 の反応式
Cl[CH2:2][C:3]([NH:5][C:6]1[S:7][C:8]2[N:9]=[C:10]([NH:15][C:16]3[CH:17]=[C:18]([NH:23][C:24](=[O:36])[C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:33])[CH3:32])[CH:26]=4)[CH:19]=[CH:20][C:21]=3[CH3:22])[N:11]=[CH:12][C:13]=2[N:14]=1)=[O:4].CN(C)C=O.C(N(CC)CC)C.[CH3:49][N:50]1[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1>O1CCCC1.O>[C:34]([C:31]([C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=1)[C:24]([NH:23][C:18]1[CH:19]=[CH:20][C:21]([CH3:22])=[C:16]([NH:15][C:10]2[N:11]=[CH:12][C:13]3[N:14]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:53]4[CH2:54][CH2:55][N:50]([CH3:49])[CH2:51][CH2:52]4)[S:7][C:8]=3[N:9]=2)[CH:17]=1)=[O:36])([CH3:32])[CH3:33])#[N:35]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 86646091N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino)-4-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide

生成物 1

HCID 595070353-(1-cyano-1-methylethyl)-N-{4-methyl-3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]phenyl}benzamide
収率 82%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a solution of N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl}amino)-4-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide (150 mg, 288 μmol) produced in Example D32(i) in tetrahydrofuran (4 mL)/N,N-dimethylformamide (0.5 mL) were added triethylamine (120 μL, 864 μmol) and 1-methylpiperazine (96 μL, 864 μmol), and the mixture was stirred at 60° C. for 3 hr. To the reaction mixture was added water (15 mL), and the mixture was extracted with ethyl acetate (20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=97/3→92/8), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from tetrahydrofuran, ethyl acetate and hexane to give the title compound (137 mg, 82%) as colorless crystals.

後処理

  1. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=97/3→92/8)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from tetrahydrofuran, ethyl acetate and hexane

出典と根拠

ORDレコード
ord-80848e274425439da22138425c94fa57
出典データセット
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08344135B2

反応ノート

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