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

HRID 613878Notes

Reaction equation

HRID 613878 reaction equation
C(OC(=O)C[C@@H](N1[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(N[C@@H](CC1C=CC=CC=1)CO)=O)C1C=CC=CC=1.FC(F)(F)C(O)=[O:48].[CH2:52]([O:59][C:60](=[O:74])[CH2:61][C@@H:62]([NH2:73])[C:63]([NH:65][CH:66]([CH2:71][OH:72])[C:67]([CH3:70])([CH3:69])[CH3:68])=[O:64])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>ClCCCl>[CH2:52]([O:59][C:60](=[O:74])[CH2:61][C@@H:62]([N:73]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](=[O:48])[NH2:43])=[CH:38][CH:37]=3)=[CH:32][CH:31]=2)=[CH:26]1)[C:63]([NH:65][C@H:66]([CH2:71][OH:72])[C:67]([CH3:70])([CH3:69])[CH3:68])=[O:64])[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

Participants

4

Reactant 2

HCID 15459675N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(4'-cyano-biphenyl4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl esterHCID 701438803(r)-Amino-n-(1-hydroxymethyl-2,2-dimethyl-propyl)succinamic acid benzyl ester trifluoroacetate salt

Product 1

HCID 700994053(R)-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]-N-(1(S)-hydroxymethyl-2,2-dimethyl-propyl)succinamic acid benzyl esterYield 41%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

As described for 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, crude 3-(4'-carboxamidobiphenyl)-2,5-dimethoxy-tetrahydrofuran and 3(R)-amino-N-(1-hydroxymethyl-2,2-dimethyl-propyl)succinamic acid benzyl ester trifluoroacetate salt were condensed in 1,2-dichloroethane to furnish 110 mg (41%) of 3(R)-[3-(4'-carbamoylbiphenyl-4-yl)-1H-pyrrol-1-yl]-N-(1(S)-hydroxymethyl-2,2-dimethyl-propyl)succinamic acid benzyl ester as a solid, mp 201-3° C. 1H NMR (CDCl3): δ 7.88 (d, 2H, J=8.1 Hz), 7.69 (d, 2H, J=8.4 Hz), 7.61 (d, 2H, J=8.4 Hz), 7.56 (d, 2H, J=8.7 Hz), 7.36-7.26 (m, 5H), 7.10 (d, 1H, J=1.9 Hz), 6.81 (d, 1H, J=2.5 Hz), 6.61 (t, 1H, J=1.6 Hz), 5.60-5.56 (m, 1H), 5.10-5.02 (m, 3H), 3.80-3.70 (m, 2H), 3.50-3.38 (m, 3H), 3.24 (dd, 1H, J=4.0, 17.0 Hz), 0.80 (s, 9H). IR KBr): 3356, 2961, 1735, 1655, 1606, 1560, 1542, 1406, 1200 cm-1. Anal. Calculated for C34H37N3O5.0.25 CH2Cl2 : C, 69.85; H, 6.42; N, 7.14. Found: C, 69.82, H, 6.67; N, 7.12.

Sources & evidence

ORD record
ord-090ab7f85a17404398562f3d91758f21
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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