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

HRID 572510ノート

反応式

HRID 572510 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](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]

参加物

5

反応物 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

生成物 1

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

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 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).

後処理

  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

出典と根拠

ORDレコード
ord-092dcaa0c797479b84501c743a43ccbe
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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