Diisopropylethylamine → (+/-)-{4-Chloro-2-[2-(2-methoxy-benzylthiocarbamoyl)-1,2,3,4-tetrahydro-isoquinolin-1-yl]-phenoxy}-acetic acid

HRID 2036203

反応式

HRID 2036203 の反応式
Cl.C([O:4][C:5](=[O:25])[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1)C.C(N(C(C)C)C(C)C)C.[CH3:35][O:36][C:37]1[CH:46]=[CH:45][CH:44]=[CH:43][C:38]=1[CH2:39][N:40]=[C:41]=[S:42]>C(Cl)Cl>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([O:7][CH2:6][C:5]([OH:4])=[O:25])=[C:9]([CH:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][CH2:17][N:16]2[C:41](=[S:42])[NH:40][CH2:39][C:38]2[CH:43]=[CH:44][CH:45]=[CH:46][C:37]=2[O:36][CH3:35])[CH:10]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 1402562-Methoxybenzyl isothiocyanateHCID 66653750(+/-)-[4-Chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride

生成物 1

HCID 86682579(+/-)-{4-Chloro-2-[2-(2-methoxy-benzylthiocarbamoyl)-1,2,3,4-tetrahydro-isoquinolin-1-yl]-phenoxy}-acetic acid

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (±)-[4-chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (76 mg, 0.20 mmol, 1.0 eq.) and N-ethyldiisopropylamine (42 μL, 0.24 mmol, 1.2 eq) in DCM (2 mL), 2-methoxybenzyl isothiocyanate (36 mg, 0.20 mmol, 1.0 eq.) was added. The resulting mixture was stirred at r.t. for 19 hours. The mixture was diluted with DCM (20 mL), washed with 10% aq. AcOH (2×5 mL) and with sat. aq. NaCl (1×5 mL). The org. layer was concentrated in vacuo. The residue was dissolved in DMF (1 mL). 1M aq. NaOH soln. (0.5 mL) was added. The mixture was stirred at r.t. for 7 hours. The solution was carefully neutralized with formic acid (0.5 mL), filtered, and purified by prep. HPLC (column: Waters X-bridge, 30×75 mm, 10 um, UV/MS, acidic conditions) to give the desired acid as a white solid.

後処理

  1. washwashed with 10% aq. AcOH (2×5 mL) and with sat. aq. NaCl (1×5 mL)
  2. concentrationlayer was concentrated in vacuo
  3. dissolutionThe residue was dissolved in DMF (1 mL)
  4. addition(0.5 mL) was added
  5. stirringThe mixture was stirred at r.t. for 7 hours
  6. filtrationfiltered
  7. custompurified by prep

出典と根拠

ORDレコード
ord-d548314e33bf465ba5d30e2eeeff4fc5
出典データセット
uspto-grants-2013_11
特許番号
US08575158B2

関連ノート

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