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Diethylamine → tert-Butyl 4-[N-[2-Diethylaminomethyl-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

HRID 47853
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HRID 47853 반응식
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[N:7]([CH3:18])[C:8]([CH2:12]OS(C)(=O)=O)=[N:9]2)=[CH:4][C:3]=1[CH2:20][N:21]([C:25]1[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:27][CH:26]=1)[CH2:22][C:23]#[CH:24].[CH2:38]([NH:40][CH2:41][CH3:42])[CH3:39]>ClCCl.C(OCC)(=O)C>[CH2:38]([N:40]([CH2:12][C:8]1[N:7]([CH3:18])[C:6](=[O:19])[C:5]2[C:10](=[CH:11][C:2]([Cl:1])=[C:3]([CH2:20][N:21]([C:25]3[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])=[CH:27][CH:26]=3)[CH2:22][C:23]#[CH:24])[CH:4]=2)[N:9]=1)[CH2:41][CH3:42])[CH3:39]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 2

HCID 8021DiethylamineHCID 11813583tert-Butyl 4-[N-[7-Chloro-2-methanesulphonyloxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

생성물 1

HCID 11114065tert-Butyl 4-[N-[2-Diethylaminomethyl-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

시약·촉매·용매 2

HCID 6344Dichloromethane용매
HCID 8857
Ethyl Acetate
용매

실험 절차

To a stirred under argon solution of tert-butyl 4-[N-[7-chloro-2-methanesulphonyloxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.230 g, 0.42 mmol) in anhydrous dichloromethane (10 ml) was added diethyl amine (0.306 g, 4.2 mmol). The yellow solution was then stirred at room temperature for 18 hours. The solution was then diluted with ethyl acetate (250 ml) and washed with 5% aqueous sodium carbonate solution (2×100 ml), brine (100 ml), and concentrated in vacuo. Purification by column chromatography, on gradient elution with methanol in dichloromethane (0 to 2%) afforded a white crispy solid which was triturated diethyl ether/hexanes (v/v, 1:2). The white solid was collected by filtration, washed with hexanes and dried in vacuo over P2O5 (0.202 g, 92%), mp 112-113° C.; 1H-NMR (DMSO-d6) 0.95 (t, J=6.9 Hz, 6H, 2×CH2CH3), 1.49 (s, 9H, But), 2.56 (q obscured, J=6.85 Hz, 4H, 2×CH2CH3), 3.62 (s, 3H, N3-Me), 3.70 (s, 2H, 2-CH2), 4.40 (s, 2H, CH2C≡C), 4.79 (s, 2H, 6-CH2), 6.78 (d, J=8.9 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.9 Hz, 2′,6′-ArH), 7.81, 7.86 (2×s, 2H, 5-H, 8-H); MS (FAB, m/z) 523, 525 [(M+H)+, 100%, 40% respectively; Cl isotopic pattern].

후처리

  1. washwashed with 5% aqueous sodium carbonate solution (2×100 ml), brine (100 ml)
  2. concentrationconcentrated in vacuo
  3. customPurification by column chromatography
  4. washon gradient elution with methanol in dichloromethane (0 to 2%)
  5. customafforded a white crispy solid which
  6. customwas triturated diethyl ether/hexanes (v/v, 1:2)
  7. filtrationThe white solid was collected by filtration
  8. washwashed with hexanes
  9. dry with materialdried in vacuo over P2O5 (0.202 g, 92%), mp 112-113° C.

출처 및 근거

ORD 기록
ord-d4a7a0d197a6451ba0b505edad115fdf
출처 데이터셋
uspto-grants-2004_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06699861B1

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