Dimethylacetamide → (R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(2-hydroxythiazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid Ethyl Ester

HRID 541506Notes

Reaction equation

HRID 541506 reaction equation
[OH:1][C:2]1[S:3][C:4]([C:7]([OH:9])=O)=[CH:5][N:6]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC(N(C)C)=O.[CH2:40]([O:42][C:43](=[O:64])[C@H:44]([OH:63])[CH2:45][N:46]([CH2:48][C:49]1[CH:54]=[CH:53][C:52]([C:55]2[CH:60]=[C:59]([Cl:61])[CH:58]=[CH:57][C:56]=2[F:62])=[CH:51][CH:50]=1)[NH2:47])[CH3:41].CCN(C(C)C)C(C)C>>[CH2:40]([O:42][C:43](=[O:64])[C@H:44]([OH:63])[CH2:45][N:46]([CH2:48][C:49]1[CH:50]=[CH:51][C:52]([C:55]2[CH:60]=[C:59]([Cl:61])[CH:58]=[CH:57][C:56]=2[F:62])=[CH:53][CH:54]=1)[NH:47][C:7]([C:4]1[S:3][C:2]([OH:1])=[N:6][CH:5]=1)=[O:9])[CH3:41]

Participants

6

Reactant 5

HCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 200616172-Oxo-2,3-dihydro-1,3-thiazole-5-carboxylic acidHCID 67972425(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid Ethyl Ester

Product 1

HCID 178472581(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(2-hydroxythiazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid Ethyl EsterYield 38.9%

Procedure

2-Hydroxy-5-thiazolecarboxylic acid (9.0 mg, 62 μmol) and HATU (28.3 mg, 74 μmol) were stirred in DMA (0.5 mL, 5 mmol) for 10 minutes. (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid ethyl ester (22.7 mg, 62 μmol) and DIPEA (32.4 μL, 186 μmol) were added, and resulting mixture was stirred at room temperature for 2 hours. The mixture was then concentrated under reduced pressure and the residue was dissolved in 50% AcOH-water (1.5 mL), filtered, purified by reverse phase preparative HPLC, and lyophilized to yield the title compound (11.9 mg, purity 96%) as a TFA salt. MS m/z [M+H]+ calc'd for C22H21ClFN3O5S, 494.09. found 494.4.

Workup

  1. customresulting mixture
  2. concentrationThe mixture was then concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in 50% AcOH-water (1.5 mL)
  4. filtrationfiltered
  5. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-217a706821344daf99baf1e7735a2ffc
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

Loading…