4-Methoxy-2,3,6-trimethylbenzenesulfonyl chloride → (3S)-4-[[1-[(1-amino-6-isoquinolinyl)methyl]-2-oxo-2-(4-morpholinyl)ethyl]amino]-3-[[(4-methoxy-2,3,6-trimethylphenyl)sulfonyl]amino]-4-oxo-butanoic acid 1,1-dimethylethylester hydrochloride

Participants

Reaction Steps

Protection of 0.23 g of amino acid 1i and subsequently coupling with morpholine according to the procedure described for 5a yielded 1,1-dimethylethyl [1-[(1-amino-6-isoquinolinyl)methyl]-2-oxo-2-(4-morpholinyl)ethylcarbamate. The procedure described for 5c was used for the deprotection of 90 mg of 1,1-dimethylethyl [1-[(1-amino-6-isoquinolinyl)methyl]-2-oxo-2-(4-morpholinyl)ethylcarbamate and coupling with 96 mg of (2S)-2-[[(4-methoxy-2,3,6-trimethylphenyl)sulfonyl]amino]butanedioic acid 4-(1,1-dimethylethyl)ester (prepared from Asp(OtBu)-OH and (4-methoxy-2,3,6-trimethylphenyl)sulfonylchloride using the procedure described for 5b) to yield the title compound (56 mg) as a mixture of diastereomers (1:1). 1H-NMR 400 MHz (CD3OD) δ: 1.29 and 1.33 (9H, 2× s), 2.12 and 2.13 (3H, 2× s), 2.19-2.47 (2H, m), 2.52 and 2.53 (3H, 2× s), 2.62 (3H, s), 2.95-3.65 (10H, m), 3.81 and 3.86 (3H, 2× s), 3.95-4.08 (1H, m), 5.03-5.18 (1H, m), 6.73 and 6.75 (1H, 2× s), 7.18-7.23 (1H, m), 7.53-7.78 (3H, m), 8.31-8.38 (1H, m).

Provenance & Evidence