Pyridine → 2(R)-[3-(4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic acid 4-benzyl ester hydrochloride

HRID 566783Notes

Reaction equation

HRID 566783 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]N=[CH:31][CH:30]=2)=[CH:25]1)[C:12](N[C@H](C(=O)NC)C(C)(C)C)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)(C)[C@H](NC(=O)[C@H](N1C=CC(C2C=C[C:56]([C:59]3[CH:64]=[CH:63][N:62]=[CH:61][CH:60]=3)=CC=2)=C1)CC(O)=O)CO.N1C=CC=CC=1.FC(F)(F)C(O)=[O:77].[Cl:81][Si](C)(C)C>ClCCCl>[ClH:81].[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][C:56]([C:59]3[CH:64]=[CH:63][N:62]=[CH:61][CH:60]=3)=[CH:31][CH:30]=2)=[CH:25]1)[C:12]([OH:77])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 6397ChlorotrimethylsilaneHCID 6422Trifluoroacetic acidHCID 15459669N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-pyridin-4-yl-1H-pyrrol-1-yl)succinamic acid benzyl esterHCID 15487948N-(2,2-dimethyl-1(S)-hydroxymethyl-propyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid

Product 1

HCID 700979932(R)-[3-(4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic acid 4-benzyl ester hydrochloride

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

According to the procedure as described in Example 1(d) for the preparation of N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-pyridin-4-yl-1H-pyrrol-1-yl)succinamic acid benzyl ester, to a solution of D-aspartate β-benzyl ester (223 mg, 1.00 mmol) and 2,5-dimethoxy-3-(4-(pyridin-4-yl)phenyl)tetrahydrofuran (350 mg, 1.20 mmol; prepared as described in Example 5(a)) in 1,2-dichloroethane was added sequentially pyridine (0.16 mL, 2.0 mmol), trifluoroacetic acid (0.08 mL, 1 mnol), and chlorotrimethylsilane (0.38 mL, 3.0 mmol). After 17 hours at 80° C., the mixture was allowed to cool to ambient temperature. Filtration led to isolation of 408 mg (87%) of 2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic acid 4-benzyl ester hydrochloride as a yellow solid, mp 203-5° C. (d). 1H NMR (DMSO-d6): δ 8.86 (d, 2H, J=6.3 Hz), 8.38 (d, 2H, J=6.6 Hz), 8.02 (d, 2H, J=8.5 Hz), 7.74 (d, 2H, J=8.5 Hz), 7.58 (s, 1H), 7.31-7.24 (m, 5H), 6.96 (t, 1H, J=2.4 Hz), 6.58 (s, 1H), 5.23 (t, 1H, J=7.4 Hz), 5.10 (s, 2H), 3.36 (dd, 1H, J=6.6, 16.6 Hz), 3.21 (dd, 1H, J=7.7, 16.9 Hz). Anal. Calculated for C26H22N2O4•HCl•0.3 H2O: C, 66.68; H, 5.08; N, 5.98; Cl, 7.57. Found: C, 66.56; H, 5.01; N, 5.98; Cl, 7.80.

Workup

  1. filtrationFiltration

Sources & evidence

ORD record
ord-ca3665d178854c08b33a051e96abe00d
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

Loading…