N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(4'-cyano-biphenyl4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl ester → N-(1-benzyl-2-hydroxyethyl)-3-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl ester

HRID 566770Notes

Reaction equation

HRID 566770 reaction equation
[CH2:1]([O:8][C:9](=[O:44])[CH2:10][C@@H:11]([N:25]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][C:39]([C:42]#[N:43])=[CH:38][CH:37]=3)=[CH:32][CH:31]=2)=[CH:26]1)[C:12]([NH:14][C@@H:15]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:16][OH:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:52]C(=O)C(N)[C@@H](C(OCCCC)=O)C(N[C@@H](CC1C=CC=CC=1)CO)=O)C1C=CC=CC=1.FC(F)(F)C(O)=O.C(OC(=O)C[C@@H](N)C(N[C@@H](CC1C=CC=CC=1)CO)=O)C1C=CC=CC=1.CO.C(Cl)Cl>ClCCCl>[CH2:1]([O:8][C:9](=[O:44])[CH2:10][CH:11]([N:25]1[CH:29]=[CH:28][C:27]([C:30]2[CH:31]=[CH:32][C:33]([C:36]3[CH:37]=[CH:38][C:39]([C:42](=[O:52])[NH2:43])=[CH:40][CH:41]=3)=[CH:34][CH:35]=2)=[CH:26]1)[C:12]([NH:14][CH:15]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:16][OH:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 15459675N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(4'-cyano-biphenyl4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl esterHCID 21226129Dichloromethane methanolHCID 70082764N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-butoxycarbonyl-amino-succinamic acid benzyl esterHCID 701436173(R)-amino-N-(l(S)-benzyl-2-hydroxyethyl)succinamic acid benzyl ester trifluoroacetate salt

Product 1

HCID 18341459N-(1-benzyl-2-hydroxyethyl)-3-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl esterYield 31%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

As described in Example 4(a) for the preparation of N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(4′-cyano-biphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl ester, N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-butoxycarbonyl-amino-succinamic acid benzyl ester (0.320 mmol) was deprotected. A solution of the resultant crude N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-amino-succinamic acid benzyl ester trifluoroacetate salt and crude 3-(4′-carboxamidobiphenyl-4-yl)-2,5-dimethoxytetrahydrofuran (110 mg, 0.330 mmol) in 1,2-dichloroethane condensed in 18 hours to give a brown solid, which was punfied via flash column chromatography with 5% MeOH/CH2Cl2 as eluant to provide 60 mg (31%) of N-(1-benzyl-2-hydroxyethyl)-3-[3-(4′-carbamoylbiphenyl4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl ester as a pale yellow solid, mp 192-4° C. 1H NMR (DMSO-d6): δ 8.18 (d, 1H, J=8.5 Hz), 8.00 (s, 1H), 7.94 (d, 2H, J=8.1 Hz), 7.76 (d, 2H, J=8.5 Hz), 7.68 (d, 2H, J=8.5 Hz), 7.58 (d, 2H, J=8.5 Hz), 7.36-7.14 (bm, 7H), 6.84 (t, 1H, J=2.2 Hz), 6.47 (s, 1H), 5.10-4.95 (m, 3H), 4.81 (t, 1H, J=5.1 Hz), 3.88-3.75 (m, 1H), 3.00 (d, 2H, J=7.4 Hz), 2.80 (dd, 1H, J=5.5, 13.2 Hz), 2.67-2.60 (m, 1H). IR (KBr): 3330, 2962, 1729, 1655, 1606, 1560, 1498, 1261, 1092 cm−1. FABMS: 602 (M+H+). Anal. Calculated for C37H35N3O5•0.4 CH2Cl2: C, 70.67; H, 5.68; N, 6.61. Found: C, 70.78; H, 5.86; N, 6.98.

Workup

  1. customto give a brown solid, which

Sources & evidence

ORD record
ord-12e3ef1feed248aa966598c8a47871b9
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

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