Tetrahydrofuran → 2-Tert-butoxy-2-[4-(3,4-dimethylphenyl)-2-methyl-7-[(oxaloamino)methyl]-1-oxo-3-isoquinolyl]acetic acid

HRID 572510노트

반응식

HRID 572510 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](OC)=[O:17])[N:9]([CH3:14])[C:10]2=[O:13])=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.Cl[C:43](=[O:48])[C:44]([O:46]C)=[O:45].[O:49]1CCCC1>>[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][C:43]([C:44]([OH:46])=[O:45])=[O:48])[CH:12]=2)[C:16]([OH:49])=[O:17])([CH3:23])([CH3:24])[CH3:22]

참가 물질

5

반응물 4

HCID 8028TetrahydrofuranHCID 79846Methyl chloroglyoxylateHCID 81531DiisopropylethylamineHCID 68295579Methyl [7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

생성물 1

HCID 682955682-Tert-butoxy-2-[4-(3,4-dimethylphenyl)-2-methyl-7-[(oxaloamino)methyl]-1-oxo-3-isoquinolyl]acetic acid수율 61.2%

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 tetrahydrofuran (THF) (1.000 mL) was treated with DIEA (0.015 mL, 0.086 mmol) and methyl 2-chloro-2-oxoacetate (6.35 μL, 0.069 mmol). After stirring for 40 min, the reaction was quenched with sat. NaHCO3, extracted with EtOAc, washed with sat. NaHCO3, Brine, dried with Na2SO4, filtered, and concentrated. The residue 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-(7-((carboxyformamido)methyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetic acid (13.7 mg, 0.026 mmol, 61.2% yield) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.32 (s, 1 H), 7.61-7.49 (m, 1 H), 7.36-7.22 (m, 2 H), 7.04-7.14 (m, 2 H), 5.26 (s, 1 H), 4.59 (s, 2 H), 3.75-3.68 (m, 3 H), 2.39 (s, 3 H), 2.34 (s, 3 H), 1.04-0.96 (m, 9 H); LCMS (m/z) ES+=495 (M+1).

후처리

  1. customthe reaction was quenched with sat. NaHCO3
  2. extractionextracted with EtOAc
  3. washwashed with sat. NaHCO3, Brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-092dcaa0c797479b84501c743a43ccbe
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029391B2

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