1-Hydroxybenzotriazole → 5-Fluoro-4-hydroxy-3-{2-[(1H-imidazole-2-carbonyl)-amino]-propionylamino}-pentanoic acid tert-butyl ester

HRID 2422339Notes

Reaction equation

HRID 2422339 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([NH:8][C@@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7].[C:14]([O:18][C:19](=[O:27])[CH2:20][CH:21]([NH2:26])[CH:22]([OH:25])[CH2:23][F:24])([CH3:17])([CH3:16])[CH3:15].C(N(C(C)C)CC)(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C1COCC1.CN(C1C=CN=CC=1)C>[C:14]([O:18][C:19](=[O:27])[CH2:20][CH:21]([NH:26][C:10](=[O:12])[CH:9]([NH:8][C:6]([C:2]1[NH:1][CH:5]=[CH:4][N:3]=1)=[O:7])[CH3:13])[CH:22]([OH:25])[CH2:23][F:24])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 108566723-Amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl esterHCID 57462012(2S)-2-[(1H-imidazole-2-carbonyl)-amino]-propionic acid

Product 1

HCID 670587205-Fluoro-4-hydroxy-3-{2-[(1H-imidazole-2-carbonyl)-amino]-propionylamino}-pentanoic acid tert-butyl esterYield 97%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (2S)-2-[(1H-imidazole-2-carbonyl)-amino]-propionic acid and 3-amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester (0.254 g) in THF (7 mL) was cooled to 0° C. before addition of DMAP (0.151 g), diisopropylethyl amine (0.56 mL), HOBT (0.16 g) and EDC HCl (0.23 g). The reaction mixture was stirred at ambient temperature for 18 hrs before being concentrated at reduced pressure. The residue was purified by silica gel chromatography (5% methanol in dichloromethane) to afford the sub-title compound as a colourless solid (0.386 g, 97%): 1H NMR 400 MHz CDCl3/CD3OD 1.40 (12H, m), 3.92 (1H, m), 4.20-4.55 (4H, m), 7.11 (2H, d, J 15); 19F NMR CDCl3−229.74 (m), −229.84 (m), −230.54 (m), −230.87 (m).

Workup

  1. concentrationbefore being concentrated at reduced pressure
  2. customThe residue was purified by silica gel chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-198dcc8cb72c4318a087693049e83de7
Source dataset
uspto-grants-2011_06
Patent number
US07960398B2

Reaction notes

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