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 540253ノート

反応式

HRID 540253 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7dc4b41ce797419c9dbff53c6e41b3de
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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