Hydrochloric Acid → 3-{[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]amino}propane-1,2-diol

HRID 540253노트

반응식

HRID 540253 반응식
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][CH:14]2[CH2:18][O:17]C(C)(C)[O:15]2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:21])[CH:8]=2)[N:3]=1.C(N(CC)CC)C.[S:29]1(=[O:41])(=[O:40])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[CH2:33][NH:32][CH2:31][CH2:30]1.Cl>CN(C)C=O.CO>[O:41]=[S:29]1(=[O:40])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[CH2:33][N:32]([C:2]2[N:11]=[C:10]([NH:12][CH2:13][CH:14]([OH:15])[CH2:18][OH:17])[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([CH3:21])[CH:8]=3)[N:3]=2)[CH2:31][CH2:30]1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 196081962,3,4,5-Tetrahydrobenzo[F][1,4]thiazepine 1,1-dioxideHCID 866914222-Chloro-N-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-6-methylquinazolin-4-amine

생성물 1

HCID 712621393-{[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]amino}propane-1,2-diol수율 10%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

A solution of 2-chloro-N-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-6-methylquinazolin-4-amine (431.2 mg, 1.4 mmol) and triethylamine (0.8 mL), 2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (296.1 mg, 1.5 mmol) in N,N-dimethyl-formamide (1.0 mL) was stirred at 160° C. for 4 hours. After being cooled to room temperature, the reaction mixture was dissolved in methanol (2.0 mL). To the above mixture, concentrated hydrochloric acid (0.5 mL) was added, and the resulting mixture was stirred at room temperature for 1 hour, and then extracted with ethyl acetate (100 mL). The organic layer was washed with brine (50 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford 59.2 mg of the product as a white solid (yield was 10%). MS obsd. (ESI+) [(M+H)+] 429, 1H NMR (400 MHz, CD3OD) δ ppm 7.98 (dd, J=7.83, 1.01 Hz, 1 H), 7.90 (d, J=7.58 Hz, 1 H), 7.66-7.55 (m, 2 H), 7.50-7.35 (m, 2 H), 7.35-7.28 (m, 1 H), 5.21 (brs, 2 H), 4.56 (brs, 2 H), 4.05-3.95 (m, 1 H), 3.86 (dd, J=13.26, 4.42 Hz, 1 H), 3.73-3.56 (m, 3 H), 3.53 (t, J=5.05 Hz, 2 H), 2.39 (s, 3 H).

후처리

  1. extractionextracted with ethyl acetate (100 mL)
  2. washThe organic layer was washed with brine (50 mL×2)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-7dc4b41ce797419c9dbff53c6e41b3de
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871756B2

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