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

HRID 636961

Reaktionsgleichung

Reaktionsgleichung von HRID 636961
Cl.NC1C2C(=CC(CC(NC(=O)CNS(C3C(C)=C(C)C4OC(C)(C)CCC=4C=3C)(=O)=O)C(=O)N3CCCCC3)=CC=2)C=CN=1.[NH2:46][C:47]1[C:56]2[C:51](=[CH:52][C:53]([CH2:57][CH:58]([NH:67][C:68](=O)[O-:69])[C:59](=[O:66])[N:60]3[CH2:65][CH2:64][O:63][CH2:62][CH2:61]3)=[CH:54][CH:55]=2)[CH:50]=[CH:49][N:48]=1.[CH3:71][C:72]([O:75][C:76](=[O:97])[CH2:77][C@H:78]([NH:82][S:83]([C:86]1[C:91]([CH3:92])=[CH:90][C:89]([O:93][CH3:94])=[C:88]([CH3:95])[C:87]=1[CH3:96])(=[O:85])=[O:84])C(O)=O)([CH3:74])[CH3:73].N[C@H](C(O)=O)CC(=O)OC(C)(C)C.COC1C=C(C)C(S([Cl:123])(=O)=O)=C(C)C=1C>>[ClH:123].[CH3:74][C:72]([O:75][C:76](=[O:97])[CH2:77][C@H:78]([NH:82][S:83]([C:86]1[C:91]([CH3:92])=[CH:90][C:89]([O:93][CH3:94])=[C:88]([CH3:95])[C:87]=1[CH3:96])(=[O:85])=[O:84])[C:68]([NH:67][CH:58]([CH2:57][C:53]1[CH:52]=[C:51]2[C:56](=[CH:55][CH:54]=1)[C:47]([NH2:46])=[N:48][CH:49]=[CH:50]2)[C:59](=[O:66])[N:60]1[CH2:61][CH2:62][O:63][CH2:64][CH2:65]1)=[O:69])([CH3:71])[CH3:73]

Komponenten

6

Edukt 5

HCID 5627874-Methoxy-2,3,6-trimethylbenzenesulfonyl chlorideHCID 70105704-tert-Butyl hydrogen L-aspartateHCID 22665631HCID 22665631, VerbindungHCID 86588684(2S)-2-[[(4-methoxy-2,3,6-trimethylphenyl)sulfonyl]amino]butanedioic acid 4-(1,1-dimethylethyl)esterHCID 865886931-[(1-Amino-6-isoquinolinyl)methyl]-2-oxo-2-(4-morpholinyl)ethylcarbamate

Produkt 1

HCID 86588691(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

Versuchsvorschrift

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, 2x s), 2.12 and 2.13 (3H, 2x s), 2.19-2.47 (2H, m), 2.52 and 2.53 (3H, 2x s), 2.62 (3H, s), 2.95-3.65 (I OH, m), 3.81 and 3.86 (3H, 2x s), 3.95-4.08 (1H, m), 5.03-5.18 (1H, m), 6.73 and 6.75 (1H, 2x s), 7.18-7.23 (1H, m), 7,53-7.78 . (3H, m), 8.31-8.38 (1H,m).

Quellen und Nachweise

ORD-Eintrag
ord-e7f7cb982a074533bc0071ccd0e82d9c
Quelldatensatz
uspto-grants-2001_02
Patentnummer
US06194409B1

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