Hydrochloric Acid → 2-Chloro-9-cyclopentyl-7-fluoro-7-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

HRID 914146ノート

反応式

HRID 914146 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:9][C:10]([F:17])([CH3:16])[C:11](OCC)=[O:12])[C:5]([N+:23]([O-])=O)=[CH:4][N:3]=1.Cl>C(O)(=O)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:23][C:11](=[O:12])[C:10]([F:17])([CH3:16])[CH2:9][N:8]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[C:6]=2[N:7]=1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 57955550Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)amino)-2-fluoro-2-methylpropanoate

生成物 1

HCID 579556652-Chloro-9-cyclopentyl-7-fluoro-7-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one収率 23.1%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
60 °C

実験手順

To a suspension of ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)amino)-2-fluoro-2-methylpropanoate (3.4 g, 9 mmol), reduced iron (1.2 g, 23 mmol) in acetic acid (20 ml) was added dropwise concentrated hydrochloric acid (2 ml) at 0° C. The reaction mixture was stirred at 60° C. for 18 h. It was then concentrated in vacuo, diluted to EtOAc, basified with 10% NaOH solution at 0° C. The whole was filtered through celite, washed with EtOAc. The filtrate was then separated. The organic layer was dried over Na2SO4. The solution was concentrated in vacuo followed by precipitation from ether to afford the product (620 mg, 23% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42-1.67 (m, 7H) 1.72 (d, J=4.0 Hz, 2H) 1.77-1.91 (m, 2H) 3.58-3.77 (m, 2H) 5.01 (t, J=8.2 Hz, 1H) 7.97 (s, 1H) 10.36 (s, 1H). [M+H] calc'd for C13H16ClFN4O, 299. found 299.

後処理

  1. concentrationIt was then concentrated in vacuo
  2. additiondiluted to EtOAc
  3. custombasified with 10% NaOH solution at 0° C
  4. filtrationThe whole was filtered through celite
  5. washwashed with EtOAc
  6. customThe filtrate was then separated
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationThe solution was concentrated in vacuo
  9. customfollowed by precipitation from ether

出典と根拠

ORDレコード
ord-5d35c6f1969745778526f210cbb8dbe4
出典データセット
uspto-grants-2011_09
特許番号
US08026234B2

反応ノート

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