Acetic Anhydride → 2-[7-(Acetamidomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-3-isoquinolyl]-2-tert-butoxy-acetic acid

HRID 572508Notes

Reaction equation

HRID 572508 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]([O:18]C)=[O:17])[N:9]([CH3:14])[C:10]2=[O:13])=[CH:5][CH:4]=1.CCN(CC)CC.[C:40](OC(=O)C)(=[O:42])[CH3:41]>ClCCl>[C:40]([NH: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]([CH3:22])([CH3:24])[CH3:23])[C:16]([OH:18])=[O:17])[N:9]([CH3:14])[C:10]2=[O:13])=[CH:5][CH:4]=1)(=[O:42])[CH3:41]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68295579Methyl [7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

Product 1

HCID 682955022-[7-(Acetamidomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-3-isoquinolyl]-2-tert-butoxy-acetic acidYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 dichloromethane (DCM) (549 μl) was treated with Et3N (15.96 μl, 0.115 mmol) and acetic anhydride (8.11 μl, 0.086 mmol), and then stirred for 3 hours. The mixture was quenched with sat. NaHCO3, extracted with DCM, washed with 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-(7-(acetamidomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)-2-(tert-butoxy)acetic acid (21.6 mg, 0.045 mmol, 85% yield) as an off-white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm, 8.37 (s, 1 H), 7.47 (t, J=7.3 Hz, 1 H), 7.39-7.29 (m, 1 H), 7.24 (d, J=7.2 Hz, 1 H), 7.13 (dd, J=8.4, 12.6 Hz, 1 H), 7.09-6.98 (m, 1 H), 6.11 (br. s., 1 H), 5.34 (s, 1 H), 4.63-4.45 (m, 2 H), 3.69 (s, 3 H), 2.36 (s, 3 H), 2.31 (s, 3 H), 2.05 (s, 3 H), 1.10-0.96 (m, 9 H); LCMS (m/z) ES+=465 (M+1).

Workup

  1. customThe mixture was quenched with sat. NaHCO3
  2. extractionextracted with DCM
  3. washwashed with brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-83954c10c4574dab85b8fe70acb5d0ad
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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