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

HRID 540203노트

반응식

HRID 540203 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
130 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2e03cf2603014fe3bce4b679231c30dd
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871756B2

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