N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl ester → 3(R)-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]-N-(2,2-dimethyl-1(S)-(N-(pyridin-4-yl)carbarnoyl)propyl]succinamic acid benzyl ester

HRID 613887Notes

Reaction equation

HRID 613887 reaction equation
[CH2:1]([O:8][C:9](=[O:35])[CH2:10][C@@H:11]([N:24]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25]1)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C[C@@H:46](NC(OC(C)(C)C)=O)[C:47]([NH:49][C@H:50](C(=O)NC1C=CN=CC=1)[C:51](C)(C)C)=O)C1C=CC=CC=1.C(C(NC(=O)[C@H](N1C=CC(C2C=CC([C:101]3[CH:106]=[CH:105][C:104]([C:107](=[O:109])[NH2:108])=[CH:103][CH:102]=3)=CC=2)=C1)CC(O)=O)CO)C1C=CC=CC=1>ClCCCl>[CH2:1]([O:8][C:9](=[O:35])[CH2:10][C@@H:11]([N:24]1[CH:28]=[CH:27][C:26]([C:29]2[CH:30]=[CH:31][C:32]([C:101]3[CH:102]=[CH:103][C:104]([C:107](=[O:109])[NH2:108])=[CH:105][CH:106]=3)=[CH:33][CH:34]=2)=[CH:25]1)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][C:22]1[CH:51]=[CH:50][N:49]=[CH:47][CH:46]=1)[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 15459665N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl esterHCID 53819559N-(1-Benzyl-2-hydroxyethyl)-3(R)-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acidHCID 570691383(R)-t-butoxycarbonylamino-N-[2,2-dimethyl-1(S)-(pyridin-4-yl)carbamoylpropyl]succinamic acid benzyl ester

Product 1

HCID 154596803(R)-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]-N-(2,2-dimethyl-1(S)-(N-(pyridin-4-yl)carbarnoyl)propyl]succinamic acid benzyl esterYield 36%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

According to the procedure described in Example 1(b) for the preparation of N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl ester, 3(R)-t-butoxycarbonylamino-N-[2,2-dimethyl-1(S)-(pyridin-4-yl)carbamoylpropyl]succinamic acid benzyl ester was deprotected. The crude amine salt and crude 3-(4'-carboxamidobiphenyl-4-yl)-2,5-dimethoxy-tetrahydrofuran (prepared as described in Example 4(b)) were condensed in wet 1,2-dichloroethane at 90-100° C. to yield 130 mg (36%) of 3(R)-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(N-(pyridin-4-yl)carbamoyl)propyl]succinamic acid benzyl ester. 1H NMR (CD3OD): δ 8.35 (bs, 2H), 7.95 (d, 2H, J=8.4 Hz), 7.72 (d, 2H, J=8.7 Hz), 7.60 (dd, 6h), J=8.7, 13.4 Hz), 7.28 (s, 5H), 6.90 (t, 1H, ZJ=2.8 Hz), 6.52 (dd, 1H, 1.6, 2.8 Hz), 5.38 (t, 1H, J=7.5 Hz), 5.12 (d, 2H, J=1.9 Hz), 4.40 (s, 1H), 1.00 (s, 9H). IR (KBr): 2725, 1735, 1664, 1510 cm-1. Anal. Calculated for C39H39N5O5.1.0 HOAc: C, 68.38; H, 6.05; N, 9.76. Found: C, 68.38, H, 6.05; N, 9.38.

Sources & evidence

ORD record
ord-ad0264c0e20d41338450d2f850ae98ce
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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