1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-Biphenyl-3-yl-4-methyl-pentanoic acid [(3R,4R,7R)-7-methyl-3-hydroxy-1-(pyridine-2-sulfonyl)-azepan-4-yl]-amide

HRID 229843Notes

Reaction equation

HRID 229843 reaction equation
[C:1]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:8](O)=[O:9])[CH:2]=1.[NH2:21][C@@H:22]1[CH2:28][CH2:27][C@@H:26]([CH3:29])[N:25]([S:30]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)(=[O:32])=[O:31])[CH2:24][C@H:23]1[OH:39].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOC(C)=O>[CH3:29][C@H:26]1[N:25]([S:30]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)(=[O:32])=[O:31])[CH2:24][C@@H:23]([OH:39])[C@H:22]([NH:21][C:8](=[O:9])[CH:7]([C:3]2[CH:2]=[C:1]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:6]=[CH:5][CH:4]=2)[CH2:11][CH:12]([CH3:14])[CH3:13])[CH2:28][CH2:27]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 218997772-Biphenyl-3-yl-4-methylpentanoic acidHCID 58665043(3R,4R,7R)-4-Amino-7-methyl-1-(pyridine-2-sulfonyl)-azepan-3-ol

Product 1

HCID 866074172-Biphenyl-3-yl-4-methyl-pentanoic acid [(3R,4R,7R)-7-methyl-3-hydroxy-1-(pyridine-2-sulfonyl)-azepan-4-yl]-amideYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Biphenyl-3-yl-4-methyl-pentanoic acid (270 mg, 1.0 mmol, preparation described in J. Am. Chem. Soc. 1997, 120, 9114), and (3R,4R,7R)-4-Amino-7-methyl-1-(pyridine-2-sulfonyl)-azepan-3-ol (320 mg, 1.0 mmol, Example 1k), EDCI (190 mg, 1.0 mmol), HOBT (135 mg, 1.0 mmol) and diisopropylethylamine (1.7 g, 0.23 ml, 1.3 mmol) in DMF (5 ml) were stirred at RT for 4 h. The reaction mixture was diluted with EtOAc (20 ml), washed with H2O, brine, dried with magnesium sulfate, filtered, concentrated in vacuo by rotary evaporation, and chromatographed (silica gel, 40% EtOAc/hexanes) to yield the title compound (330 mg, 62%): 1H NMR (400 MHz, CDCl3): δ 8.55-8.60 (m, 1H), 8.00 (t, 1H), 7.80-7.90 (m, 1H), 7.65 (d, 2H), 7.25-7.55 (m, 8H), 5.50-5.60 (m, 1H), 4.00-4.10 (m, 1H), 3.70-3.85 (m, 1H), 3.50-3.70 (m, 2H), 2.90-3.05 (m, 1H), 2.00-2.10 (m, 2H), 1.30-1.85 (m, 5H), 0.90-0.95 (d, 9H); ESMS: 536.4 (M+H+)

Workup

  1. washwashed with H2O, brine
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo by rotary evaporation
  5. customchromatographed (silica gel, 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e6dbaee1399d4ae483c248ff799cee9e
Source dataset
uspto-grants-2009_07
Patent number
US07563784B2

Reaction notes

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