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

HRID 382145Notes

Reaction equation

HRID 382145 reaction equation
[CH2:1]([O:8][C:9](=[O:35])[CH2:10][C@@H:11]([N:24]1[CH:28]=[CH:27][C:26](C2C=CN=CC=2)=[CH:25]1)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C[C@@H](N1[CH:63]=[CH:62][C:61]([C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)=C1)C(N[C@H](C(=O)NC)C(C)(C)C)=O)C1C=CC=CC=1.COC1C(C2C=CC(CCC)=CC=2)CC(OC)O1.Cl[Si](C)(C)C>ClCCCl>[CH2:1]([O:8][C:9](=[O:35])[CH2:10][C@@H:11]([N:24]1[CH:28]=[CH:27][C:26]([C:67]2[CH:68]=[CH:69][C:64]([CH2:61][CH2:62][CH3:63])=[CH:65][CH:66]=2)=[CH:25]1)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:17])[CH3:18])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 15459665N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl esterHCID 15459669N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-pyridin-4-yl-1H-pyrrol-1-yl)succinamic acid benzyl esterHCID 183803452,5-Dimethoxy-3-(4-propylphenyl)-tetrahydrofuran

Product 1

HCID 54127116N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]-3(R)-[3-(4-propylphenyl)-1H-pyrrol-1-yl]succinamic acid benzyl esterYield 7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

As described in Example 1(d) for the preparation of N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(R)-(3-pyridin4-yl-1H-pyrrol-1-yl)succinamic acid benzyl ester, 3(R)-amino-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid benzyl ester trifluoroacetate salt (prepared as described in Example 1(b); 522 mg, 1.16 mmol) was condensed with crude 2,5-dimethoxy-3-(4-propylphenyl)-tetrahydrofuran (1.29 mmol) in 1,2-dichloroethane with chlorotrimethylsilane at 90° C. over 3 days. The crude dark oil was purified via flash column chromatography with 1% HOAc/10% MeOH/CH2Cl2 as eluant to provide 40 mg (7%) of N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]-3(R)-[3-(4-propylphenyl)-1H-pyrrol-1-yl]succinamic acid benzyl ester as a solid, mp 63-5° C.:

Workup

  1. customThe crude dark oil was purified via flash column chromatography with 1% HOAc/10% MeOH/CH2Cl2 as eluant

Sources & evidence

ORD record
ord-a0425217f2cd40518cc439859fb8e656
Source dataset
uspto-grants-2001_10
Patent number
US06306892B1

Reaction notes

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