Triethylamine → methyl 2-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-7-(((N,N-dimethylsulfamoyl)amino)methyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate

HRID 572512ノート

反応式

HRID 572512 の反応式
[NH2:1][CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([CH3:32])[CH:26]=3)=[C:8]([CH:15]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:16]([O:18][CH3:19])=[O:17])[N:9]([CH3:14])[C:10]2=[O:13])=[CH:5][CH:4]=1.CCN(CC)CC.[CH3:40][N:41]([CH3:46])[S:42](Cl)(=[O:44])=[O:43]>ClCCl>[C:21]([O:20][CH:15]([C:8]1[N:9]([CH3:14])[C:10](=[O:13])[C:11]2[C:6]([C:7]=1[C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([CH3:32])[CH:26]=1)=[CH:5][CH:4]=[C:3]([CH2:2][NH:1][S:42](=[O:44])(=[O:43])[N:41]([CH3:46])[CH3:40])[CH:12]=2)[C:16]([O:18][CH3:19])=[O:17])([CH3:22])([CH3:23])[CH3:24]

参加物

5

反応物 3

HCID 8471Triethylamine2 回HCID 83372Dimethylsulphamoyl chloride2 回HCID 68295579Methyl [7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

生成物 1

HCID 68295860methyl 2-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-7-(((N,N-dimethylsulfamoyl)amino)methyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate収率 73.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

An ice cold solution of methyl 2-(7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)-2-(tert-butoxy)acetate (25 mg, 0.057 mmol) in dichloromethane (DCM) (1 mL) was treated with Et3N (0.012 mL, 0.086 mmol) and dimethylsulfamoyl chloride (7.33 μL, 0.069 mmol), stirred for 15 min, and then warmed to rt for 1 hour. Additional Et3N (25 uL) and dimethylsulfamoyl chloride (15 uL) were added, the reaction was stirred at rt overnight. The reaction was concentrated and purified by column chromatography (0-10% MeOH/DCM) to afford methyl 2-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-7-(((N,N-dimethylsulfamoyl)amino)methyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate (22.6 mg, 0.042 mmol, 72.6% yield) as clear oil. The methyl ester was hydrolyzed in a manner similar to that described in Example 165 Step C and purified by reverse phase HPLC to afford 2-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-7-(((N,N-dimethylsulfamoyl)amino)methyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetic acid (18.4 mg, 0.034 mmol, 82% yield) as white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.42 (s, 1 H), 7.54 (td, J=1.9, 8.2 Hz, 1 H), 7.41-7.30 (m, 1 H), 7.30-7.23 (m, 1 H), 7.16 (dd, J=8.4, 12.9 Hz, 1 H), 7.09-6.99 (m, 1 H), 5.35 (s, 1 H), 4.53 (br. s., 1 H), 4.36 (br. s., 2 H), 3.69 (d, J=1.0 Hz, 3 H), 2.81 (s, 3 H), 2.80 (s, 3 H), 2.36 (s, 3 H), 2.32 (s, 3 H), 1.07 (s, 4.5 H), 1.06 (s, 4.5 H); LCMS (m/z) ES+=530 (M+1).

後処理

  1. stirringthe reaction was stirred at rt overnight
  2. concentrationThe reaction was concentrated
  3. custompurified by column chromatography (0-10% MeOH/DCM)

出典と根拠

ORDレコード
ord-29d257404fb94c3bac8e9545e30ba3c2
出典データセット
uspto-grants-2015_05
特許番号
US09029391B2

反応ノート

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