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 1279063Notes

Reaction equation

Cl.NC1C2C(=CC(CC(N[C:24](=O)[CH2:25][NH:26][S:27]([C:30]3[C:31]([CH3:44])=[C:32]([CH3:43])[C:33]4[O:38][C:37](C)(C)CC[C:34]=4[C:41]=3[CH3:42])(=[O:29])=[O:28])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.N[C@H](C(O)=O)C[C:74](=[O:80])[O:75][C:76]([CH3:79])([CH3:78])[CH3:77].COC1C=C(C)C(S([Cl:96])(=O)=O)=C(C)C=1C>>[ClH:96].[CH3:77][C:76]([O:75][C:74](=[O:80])[CH2:24][C@H:25]([NH:26][S:27]([C:30]1[C:41]([CH3:42])=[CH:34][C:33]([O:38][CH3:37])=[C:32]([CH3:43])[C:31]=1[CH3:44])(=[O:28])=[O:29])[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])([CH3:79])[CH3:78]

Participants

Reactant 4

HCID 5627874-Methoxy-2,3,6-trimethylbenzenesulfonyl chloride

HCID 70105704-tert-Butyl hydrogen L-aspartate

HCID 22665631N-[1-[(1-Amino-6-isoquinolinyl)methyl]-2-oxo-2-(1-piperidinyl)ethyl]-2-[[(3,4-dihydro-2,2,5,7,8-pentamethyl-2H-1-benzopyran-6-yl)sulfonyl]amino]acetamide hydrochloride

HCID 865886931-[(1-Amino-6-isoquinolinyl)methyl]-2-oxo-2-(4-morpholinyl)ethylcarbamate

Product 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

Procedure

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-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).

Sources & evidence

ORD record: ord-f8014221d4ab49aca65a6d2612549a3b
Source dataset: uspto-grants-2002_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06444672B1

Reaction notes

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