Trifluoroacetic acid → 3(R)-(3-biphenyl-4-yl-1H-pyrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid benzyl ester

HRID 613860Notes

Reaction equation

HRID 613860 reaction equation
[CH2:1]([O:8][C:9](=[O:27])[CH2:10][C@@H:11]([NH2:26])[C:12]([NH:14][C@H:15]([C:20](=[O:25])[N:21]([O:23][CH3:24])[CH3:22])[CH2:16][CH:17]([CH3:19])[CH3:18])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:33]=[CH:32][C:31]([CH:34]2[CH2:38][CH:37](OC)O[CH:35]2OC)=[CH:30][CH:29]=1.FC(F)(F)C(O)=O>ClCCCl>[CH2:1]([O:8][C:9](=[O:27])[CH2:10][C@@H:11]([N:26]1[CH:37]=[CH:38][C:34]([C:31]2[CH:32]=[CH:33][C:28]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:29][CH:30]=2)=[CH:35]1)[C:12]([NH:14][C@H:15]([C:20](=[O:25])[N:21]([O:23][CH3:24])[CH3:22])[CH2:16][CH:17]([CH3:18])[CH3:19])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 183803263-Biphenyl-4-yl-2,5-dimethoxytetrahydrofuranHCID 542082503(R)-amino-N-(1(S)-(N-methoxy-N-methylcarbamoyl)-3-methylbutyl)succinamic acid benzyl ester

Product 1

HCID 599245073(R)-(3-biphenyl-4-yl-1H-pyrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid benzyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

As described in Example 1(c) for the preparation of N-(8-oxo-4-oxa-1,7-diaza-tricyclo-[9.6.1.012,17 ]-octadeca-11(18),12,14,16-tetraen-9-yl)-3-(3-phenyl-1H-pyrrol-1-yl acid benzyl ester, 3(R)-amino-N-(1(S)-(N-methoxy-N-methylcarbamoyl)-3-methylbutyl)succinamic acid benzyl ester was deprotected. The crude amine salt and 3-biphenyl-4-yl-2,5-dimethoxy-tetrahydrofuran (prepared as described in Example 1(a)) were condensed in anhydrous 1,2-dichloroethane with trifluoroacetic acid to provide in 48% yield 3(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid benzyl ester as an amorphous solid. 1H NMR (CDCl3): δ 7.62 (d, 2H, J=7.4 Hz), 7.58 (s, 3H), 7.44 (t, 2H, J=7.7 Hz), 7.35-7.21 (m, 7H), 7.10 (s, 1H), 6.80 (t, 1H, J=2.2 Hz), 6.60 (bs, 1H), 5.17-1.13 (m, 1H), 5.10 (s, 2H), 4.97-4.92 (m, 1H), 3.77 (s, 3H), 3.44 (dd, 1H, J=5.7, 17.1 Hz), 3.17 (s, 3H), 3.03 (dd, 1H, J=8.8, 16.5 Hz), 1.67-1.36 (m, 3H), 0.92 (d, 3H, J=6.25 Hz), 0.87 (d, 3H, J=6.3 Hz). Anal. Calculated for C35H39N3O5 : C, 72.27; H, 6.76; N, 7.22. Found: C, 72.19; H, 6.78; N, 7.16.

Sources & evidence

ORD record
ord-b3bfbce505eb4d84a1fc4cd0ede7b58a
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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