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 572512노트

반응식

HRID 572512 반응식
[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]

참가 물질

5

반응물 3

HCID 8471Triethylamine2회HCID 83372Dimethylsulphamoyl chloride2회HCID 68295579Methyl [7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

생성물 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)acetate수율 73.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-29d257404fb94c3bac8e9545e30ba3c2
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029391B2

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