Triethylamine → 2-(4-Cyano-phenyl)-N-{5-[7-(1-hydroxymethyl-cyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl]-pyridin-3-yl}-acetamide

HRID 82130

反応式

HRID 82130 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1)#[N:2].[NH2:13][C:14]1[CH:15]=[C:16]([C:20]([C:22]2[C:30]3[CH:29]=[N:28][CH:27]=[N:26][C:25]=3[N:24]([C:31]3([CH2:34][O:35]C4CCCCO4)[CH2:33][CH2:32]3)[CH:23]=2)=[O:21])[CH:17]=[N:18][CH:19]=1.CCCP(O)(O)=O.C(N(CC)CC)C>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]([NH:13][C:14]2[CH:19]=[N:18][CH:17]=[C:16]([C:20]([C:22]3[C:30]4[CH:29]=[N:28][CH:27]=[N:26][C:25]=4[N:24]([C:31]4([CH2:34][OH:35])[CH2:33][CH2:32]4)[CH:23]=3)=[O:21])[CH:15]=2)=[O:12])=[CH:7][CH:8]=1)#[N:2]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 795874-Cyanophenylacetic acidHCID 204484Propylphosphonic acidHCID 70817578(5-Amino-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone

生成物 1

HCID 708171802-(4-Cyano-phenyl)-N-{5-[7-(1-hydroxymethyl-cyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl]-pyridin-3-yl}-acetamide収率 58%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
25 °C

実験手順

(4-Cyano-phenyl)-acetic acid (6.1 mg, 0.04 mmol) was added to a solution of (5-Amino-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone (15 mg, 0.04 mmol) (Preparation 251) in THF (1 mL). Then 1-propylphosphonic acid cyclic anhydride (0.07 mL, 0.11 mmol) and triethylamine (0.02 mL, 0.13 mmol) were added and the mixture was stirred at 25° C. for 4 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL) and extracted with ethyl acetate (3×5 mL). The combined organic layer was washed with water (5 mL), brine (5 mL), dried over sodium sulphate and evaporated in vacuo. The crude was dissolved in methanol (1 mL), PTSA (5 mg) was added and stirred at room temperature for 16 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL) and extracted with dichloromethane (5×5 mL). The combined organic layer was washed with brine (5 mL), dried over sodium sulphate and evaporated in vacuo. The crude material was purified by preparative TLC (dichloromethane:methanol 95:5) to afford the title compound as a white solid in 58% yield, 10 mg.

後処理

  1. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL)
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. washThe combined organic layer was washed with water (5 mL), brine (5 mL)
  4. dry with materialdried over sodium sulphate
  5. customevaporated in vacuo
  6. dissolutionThe crude was dissolved in methanol (1 mL)
  7. additionPTSA (5 mg) was added
  8. stirringstirred at room temperature for 16 hours
  9. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL)
  10. extractionextracted with dichloromethane (5×5 mL)
  11. washThe combined organic layer was washed with brine (5 mL)
  12. dry with materialdried over sodium sulphate
  13. customevaporated in vacuo
  14. customThe crude material was purified by preparative TLC (dichloromethane:methanol 95:5)

出典と根拠

ORDレコード
ord-cff01c6468024258a775d136e338733e
出典データセット
uspto-grants-2014_09
特許番号
US08846698B2

関連ノート

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