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 914146노트

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HRID 914146 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 176Acetic Acid용매

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온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5d35c6f1969745778526f210cbb8dbe4
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026234B2

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