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

HRID 566776Notes

Reaction equation

HRID 566776 reaction equation
C(OC(=O)C[C@@H](N1C=CC(C2C=CC=CC=2)=C1)C(N[C@H](C(=O)NC)C(C)(C)C)=O)C1C=CC=CC=1.[CH2:36]([O:43][C:44](=[O:77])[CH2:45][C@@H:46]([NH:69][C:70](OC(C)(C)C)=O)[C:47]([NH:49][C@@H:50]([C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[CH2:51][O:52][C:53]([O:55][CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)=[O:54])=[O:48])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CC(C)(C)[C@H](NC(=O)[C@H](N1C=[CH:93][C:92]([C:95]2[CH:100]=[CH:99][C:98]([C:101]3[CH:106]=[CH:105][N:104]=[CH:103][CH:102]=3)=[CH:97][CH:96]=2)=[CH:91]1)CC(O)=O)CO.CO.C(Cl)Cl>ClCCCl>[CH2:36]([O:43][C:44](=[O:77])[CH2:45][C@@H:46]([N:69]1[CH:70]=[CH:91][C:92]([C:95]2[CH:100]=[CH:99][C:98]([C:101]3[CH:106]=[CH:105][N:104]=[CH:103][CH:102]=3)=[CH:97][CH:96]=2)=[CH:93]1)[C:47]([NH:49][C@@H:50]([C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[CH2:51][O:52][C:53]([O:55][CH2:56][C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1)=[O:54])=[O:48])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 15459665N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-(3-phenyl-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 acidHCID 21226129Dichloromethane methanolHCID 54557055N-(2-benzyloxycarbonyloxy-1(S)-phenyl-ethyl)-3(R)-(t-butoxycarbonylamino)succinamic acid benzyl ester

Product 1

HCID 15459678N-(2-benzyloxycarbonyloxy-1(S)-phenylethyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl esterYield 56%

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, N-(2-benzyloxycarbonyloxy-1(S)-phenyl-ethyl)-3(R)-(t-butoxycarbonylarnino)succinamic acid benzyl ester and 2,5-dimethoxy-3-(4-pyridin-4-yl-phenyl)-tetrahydrofuran (prepared as described in Example 5(a)) were condensed in wet 1,2-dichloroethane at 80-90° C. after 18 hours. Flash column chromatagraphy with 4% MeOH/CH2Cl2 as eluant gave 140 mg (56%) of N-(2-benzyloxycarbonyloxy-1(S)-phenylethyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester as a yellow solid, mp 138-40° C. 1H NMR (CDCl3): δ 8.66 (bs, 2H), 7.60 (s, 5H), 7.50 (d, 3H, J=5.3 Hz), 7.34-7.22 (m, 10H), 7.19 (d, 1H, J=2.2 Hz), 7.17 (d, 1H, J=1.9 Hz), 7.09 (t, 1H, J=1.9 Hz), 6.77 (dd, 1H, J=2.5, 2.8 Hz), 6.57 (bt, 1H, J=1.9, 2.5 Hz), 6.24 (d, 1H, J=7.8 Hz), 5.26 (m, 1H), 4.25 (dd, 1H, J=7.2, 11.5 Hz), 3.44 (dd, 1H, J=7.2, 16.8 Hz), 3.00 (dd, 1H, 8.7, 16.8 Hz). IR (KBr): 2985, 1738, 1657, 1598, 1560, 1495, 1202, 815, 697 cm−1. HRFABMS: Calculated for C42H37N3O6Cs (M+Cs+): 812.1737. Found: 812.1712. Anal. Calculated for C42H37N3O6•0.25 CHCl3: C, 71.51; H, 5.29. Found: C, 71.72; H, 5.60.

Sources & evidence

ORD record
ord-f3badbc478b3430999f3687280f76a2f
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

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