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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
ノート
印刷プレビュー

反応式

HRID 47853 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒
HCID 8857
Ethyl Acetate
溶媒

実験手順

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].

後処理

  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.

出典と根拠

ORDレコード
ord-d4a7a0d197a6451ba0b505edad115fdf
出典データセット
uspto-grants-2004_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06699861B1

反応ノート

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