Dichloromethane → (S)-2-Methoxycarbonylamino-3-methylbutyric acid 3-acetyl-5-[N'-((R)-2-carboxy-2-hydroxyethyl)-N'-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazinocarbonyl]pyrazol-1-ylmethyl Ester

HRID 541545Notes

Reaction equation

HRID 541545 reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([C:9]([NH:11][N:12]([CH2:28][C@H:29]([C:31]([OH:33])=[O:32])[OH:30])[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[F:27])=[CH:16][CH:15]=2)=[O:10])[N:6]([CH2:34][O:35][C:36](=[O:42])[C@@H:37]([NH2:41])[CH:38]([CH3:40])[CH3:39])[N:5]=1)(=[O:3])[CH3:2].C(Cl)Cl.CCN(CC)CC.Cl[C:54]([O:56][CH3:57])=[O:55]>>[C:1]([C:4]1[CH:8]=[C:7]([C:9]([NH:11][N:12]([CH2:28][C@H:29]([C:31]([OH:33])=[O:32])[OH:30])[CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[F:27])=[CH:18][CH:19]=2)=[O:10])[N:6]([CH2:34][O:35][C:36](=[O:42])[C@@H:37]([NH:41][C:54]([O:56][CH3:57])=[O:55])[CH:38]([CH3:39])[CH3:40])[N:5]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 117669070(S)-2-Amino-3-methylbutyric Acid 3-Acetyl-5-[N'-((R)-2-carboxy-2-hydroxyethyl)-N'-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazinocarbonyl]pyrazol-1-ylmethyl Ester

Product 1

HCID 117669068(S)-2-Methoxycarbonylamino-3-methylbutyric acid 3-acetyl-5-[N'-((R)-2-carboxy-2-hydroxyethyl)-N'-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazinocarbonyl]pyrazol-1-ylmethyl EsterYield 3%

Procedure

(S)-2-Amino-3-methylbutyric acid 3-acetyl-5-[N′-((R)-2-carboxy-2-hydroxyethyl)-N′-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazinocarbonyl]pyrazol-1-ylmethyl ester (21.0 mg, 35 μmol) was combined with DCM (134 μL, 2.1 mmol) and Et3N (15 μL, 0.1 mmol). Methyl chloroformate (2.7 μL, 35 μmol) was added and the mixture was stirred at room temperature for 20 minutes. The solvent was removed in vacuo and the residue was purified by preparative HPLC to yield the title compound (0.7 mg). MS m/z [M+H]+ calc'd for C30H33ClFN5O9, 662.20. found 662.1.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-aa85ac39382349f49a748c1bd2640e57
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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