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

HRID 1800738ノート

反応式

HRID 1800738 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.Cl.[F:50][C:51]1([F:57])[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]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:54]4[CH2:55][CH2:56][C:51]([F:57])([F:50])[CH2:52][CH2:53]4)[S:7][C:8]=3[N:9]=2)[CH:17]=1)=[O:36])([CH3:33])[CH3:32])#[N:35]

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 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 595069793-(1-cyano-1-methylethyl)-N-{3-[(2-{[(4,4-difluoropiperidin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]-4-methylphenyl}benzamide収率 47.1%

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 (180 μL, 1.30 mmol) and 4,4-difluoropiperidine hydrochloride (68 mg, 432 μmol), and the mixture was stirred at 60° C. for 7 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 (hexane/ethyl acetate=20/80→0/100), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate to give the title compound (82 mg, 47%) 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 (hexane/ethyl acetate=20/80→0/100)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from ethyl acetate

出典と根拠

ORDレコード
ord-b6eff13cd8794bb7995f1223607435ee
出典データセット
uspto-grants-2013_01
特許番号
US08344135B2

反応ノート

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