Water → N-[(3-Aminooxetan-3-yl)methyl]-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine

HRID 540203ノート

反応式

HRID 540203 の反応式
[NH2:1][C:2]1([CH2:6][NH:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10](Cl)[N:9]=2)[CH2:5][O:4][CH2:3]1.[S:19]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[CH2:23][NH:22][CH2:21][CH2:20]1.C(N(CC)CC)C.O>CN(C)C=O>[NH2:1][C:2]1([CH2:6][NH:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]([N:22]3[CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[S:19][CH2:20][CH2:21]3)[N:9]=2)[CH2:5][O:4][CH2:3]1

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 122691062,3,4,5-Tetrahydrobenzo[f][1,4]thiazepineHCID 86691405N-[(3-Aminooxetan-3-yl)methyl]-2-chloroquinazolin-4-amine

生成物 1

HCID 71254708N-[(3-Aminooxetan-3-yl)methyl]-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine収率 14.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
130 °C

実験手順

To a solution of N-[(3-aminooxetan-3-yl)methyl]-2-chloroquinazolin-4-amine (200 mg, 0.756 mmol) in N,N-dimethylformamide (4 mL) was added 2,3,4,5-tetrahydro-1,4-benzothiazepine (125 mg, 0.756 mmol) and triethylamine (230 mg, 2.268 mmol). After being heated at 130° C. for 4 hours under microwave irradiation, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried with sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford 42 mg of the desired product as a white solid (yield was 14%). MS obsd. (ESI+) [(M+H)+] 394, 1H NMR (400 MHz, CD3OD) δ ppm 7.75-7.73 (t, J=6.4, 1.2 Hz, 1 H), 7.56-7.53 (m, 1 H), 7.52-7.47 (m, 2 H), 7.43-7.41 (d, J=8.0 Hz, 1 H), 7.24-7.20 (m, 1 H), 7.15-7.08 (m, 2 H), 5.06 (s, 2 H), 4.69-4.67 (d, J=6.8 Hz, 2 H), 4.55-4.53 (d, J=6.4 Hz, 2 H), 4.42 (s, 2 H), 4.09 (s, 2 H), 2.97-2.95 (t, J=4.8, 4.4 Hz, 2 H).

後処理

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried with sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-2e03cf2603014fe3bce4b679231c30dd
出典データセット
uspto-grants-2014_10
特許番号
US08871756B2

反応ノート

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