Triethylamine → HCID 68867633, compound

HRID 1245120Notes

Reaction equation

HRID 1245120 reaction equation
[NH2:1][C:2]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:3]=1[C:4]([NH:6][C@@H:7]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:14][CH:13]=1)[C:8]([OH:10])=[O:9])=[O:5].[CH3:36]OC(=O)[C@@H](N)CC1C=CC(C2C=CC=CC=2OC2C=CC=CC=2)=CC=1.NC1C=CC(Cl)=CC=1C(O)=O.[CH3:73][S:74][C:75]1[CH:80]=[CH:79][C:78](B(O)O)=[CH:77][CH:76]=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:36][O:9][C:8](=[O:10])[CH:7]([NH:6][C:4](=[O:5])[C:3]1[CH:31]=[C:32]([Cl:35])[CH:33]=[CH:34][C:2]=1[NH:1][C:78]1[CH:79]=[CH:80][C:75]([S:74][CH3:73])=[CH:76][CH:77]=1)[CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 124762-Amino-5-chlorobenzoic acidHCID 27339594-(Methylthio)phenylboronic acidHCID 58717858HCID 58717858, compoundHCID 68867678HCID 68867678, compound

Product 1

HCID 68867633HCID 68867633, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8895Cupric acetateCatalyst

Procedure

A solution of (2S)-(2-amino-5-chloro-benzoylamino)-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid (0.154 g, 0.307 mmol), prepared by reacting (2S)-amino-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester and 2-amino-5-chlorobenzoic acid by the general procedure A) was reacted with 4-(methylthio)phenylboronic acid (0.130 g, 0.768 mmol), copper acetate (0.084 g, 0.460 mmol), and triethyl amine (0.215 mL, 1.535 mmol) by the general procedure G. The crude product was purified by flash column chromatography on silica gel using DCM (+25% hexane) to give 0.075 g (39%) of 2-[5-chloro-2-(4-methylsulfanyl-phenylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester as a colorless oil. This ester was treated with LiOH (0.019 g, 0.441 mmol) by the general procedure I to give 0.049 g (92%) of 2-[5-chloro-2-(4-methylsulfanyl-phenylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid. LCMS: 610 (M+1)+. 1H NMR (CDCl3) 8.94 [bs, 1H], 7.49 [d, 2H], 7.47 [d, 1H], 7.22 [m, 10H], 7.06 [d, 2H], 6.99 [d, 2H], 6.88 [d, 2H], 6.50 [d, 1H], 4.99 [m, 1H], 3.30 [m, 2H], 2.45 [s, 3H].

Workup

  1. customThe crude product was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-9928999305e64d3a9b9f5b80cdec0012
Source dataset
uspto-grants-2006_10
Patent number
US07122580B2

Reaction notes

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