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

HRID 572510Notes

Reaction equation

HRID 572510 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-092dcaa0c797479b84501c743a43ccbe
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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