1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid 5-Methyl-2-oxo-[1,3]-dioxol-4-ylmethyl Ester

HRID 541508Notes

Reaction equation

HRID 541508 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH3:22][C:23]1[O:27][C:26](=[O:28])[O:25][C:24]=1[CH2:29][O:30][C:31](=[O:52])[C@H:32]([OH:51])[CH2:33][N:34]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[CH:48]=[C:47]([Cl:49])[CH:46]=[CH:45][C:44]=2[F:50])=[CH:39][CH:38]=1)[NH2:35].[F:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[C:60]1[CH:64]=[C:63]([C:65](O)=[O:66])[O:62][N:61]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:22][C:23]1[O:27][C:26](=[O:28])[O:25][C:24]=1[CH2:29][O:30][C:31](=[O:52])[C@H:32]([OH:51])[CH2:33][N:34]([CH2:36][C:37]1[CH:38]=[CH:39][C:40]([C:43]2[CH:48]=[C:47]([Cl:49])[CH:46]=[CH:45][C:44]=2[F:50])=[CH:41][CH:42]=1)[NH:35][C:65]([C:63]1[O:62][N:61]=[C:60]([C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=2[F:53])[CH:64]=1)=[O:66]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 31602553-(2-Fluorophenyl)-1,2-oxazole-5-carboxylic acidHCID 86705088(R)-3-[N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester

Product 1

HCID 86705087(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid 5-Methyl-2-oxo-[1,3]-dioxol-4-ylmethyl EsterYield 37.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDCI (92 mg, 480 μmol) and HOBT (65 mg, 480 μmol) were added to a solution of (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester (108 mg, 240 μmol) and 3-(2-fluorophenyl)isoxazole-5-carboxylic acid (50 mg, 240 μmol) in DMF (20 mL). DIPEA (62 mg, 480 μmol) was added and the mixture was stirred for 5 hours at room temperature. The mixture was washed with saturated aqueous NaCl (2×30 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (hexanes/EtOAc=1:1) to yield the title compound as a white solid (58 mg). LC-MS: 640.2 [M+H]+. 1H-NMR: (CDCl3) 2.07 (s, 3H), 3.43 (br, 2H), 4.4-4.2 (m, 2H), 4.3 (br, 1H), 4.94-4.86 (m, 2H), 7.24-6.85 (m, 5H), 7.97-7.27 (m, 8H).

Workup

  1. washThe mixture was washed with saturated aqueous NaCl (2×30 mL)
  2. extractionextracted with EtOAc (2×50 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (hexanes/EtOAc=1:1)

Sources & evidence

ORD record
ord-ed370128eaae4b2c93c7d76c572c44c5
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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