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 1880917노트

반응식

HRID 1880917 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

반응 조건

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, 7 H) 1.72 (d, J=4.0 Hz, 2 H) 1.77-1.91 (m, 2 H) 3.58-3.77 (m, 2 H) 5.01 (t, J=8.2 Hz, 1 H) 7.97 (s, 1 H) 10.36 (s, 1 H). [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-282cf768c7484f2192e91e566002603c
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08318727B2

반응 노트

불러오는 중…