1,2-Dichloroethane → (R)-3-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid 2-Morpholin-4-ylethyl Ester

HRID 541539Notes

Reaction equation

HRID 541539 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:9]([NH:11][N:12]([CH2:28][C@@H:29]([OH:33])[C:30]([OH:32])=[O:31])[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])[NH:7][N:8]=1)(=[O:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(Cl)Cl.[N:51]1([CH2:57][CH2:58]O)[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1>>[N:51]1([CH2:57][CH2:58][O:31][C:30](=[O:32])[C@H:29]([OH:33])[CH2:28][N:12]([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)[NH:11][C:9]([C:6]2[NH:7][N:8]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=2)=[O:10])[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 6344DichloromethaneHCID 611632-MorpholinoethanolHCID 757711-HydroxybenzotriazoleHCID 86705116(R)-3-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid

Product 1

HCID 86705115(R)-3-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid 2-Morpholin-4-ylethyl EsterYield 14.8%

Procedure

(R)-3-[N′-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydr oxy-propionic acid (41.0 mg, 86 μmol), HOBt (70.0 mg, 518 μmol) and EDC (92 μL, 520 μmol) were combined in DCM (0.7 mL, 10 mmol). The resulting solution was stirred for 10 minutes. 4-Morpholineethanol (84 μL, 691 μmol) was added, and the mixture was stirred at room temperature until the reaction was complete (≈2 hours). The mixture was concentrated by rotary evaporation and purified (reverse phase column) to yield the title compound (7.5 mg, purity 98%) as a TFA salt. MS m/z [M+H]+calc'd for C28H31ClFN5O6, 588.19. found 588.1.

Workup

  1. stirringthe mixture was stirred at room temperature until the reaction
  2. custom(≈2 hours)
  3. concentrationThe mixture was concentrated by rotary evaporation
  4. custompurified (reverse phase column)

Sources & evidence

ORD record
ord-9cc6ae58f62a48009f65dc948e493711
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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