2-Oxobutanoic Acid → HCID 78324881, compound

HRID 1486638Notes

Reaction equation

HRID 1486638 reaction equation
C([O:3][C:4](=[O:24])[C@H:5]([OH:23])[CH2:6][C@H:7]([NH2:22])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:11][CH:10]=1)C.[O:25]=[C:26]([CH2:30][CH3:31])[C:27](O)=[O:28].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Li+].[OH-]>CN(C=O)C>[Cl:21][C:17]1[CH:16]=[C:15]([C:12]2[CH:11]=[CH:10][C:9]([CH2:8][C@@H:7]([NH:22][C:27](=[O:28])[C:26](=[O:25])[CH2:30][CH3:31])[CH2:6][C@@H:5]([OH:23])[C:4]([OH:3])=[O:24])=[CH:14][CH:13]=2)[CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 5

HCID 582-Oxobutanoic AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86682253(2R,4R)-4-amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester

Product 1

HCID 78324881HCID 78324881, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R,4R)-4-Amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (50 mg, 144 μmol) was added to a solution of 2-oxo-butyric acid (1.2 eq., 165 μmol) and HATU (71.1 mg, 187 μmol) in DMF (250 μL), followed by the addition of DIPEA (75 μL, 431 μmol). The resulting mixture was stirred at room temperature for 1 hour. 10 M aqueous LiOH (115 μL, 1.2 mmol) was added and the mixture was stirred for an additional 1 hour. The mixture was washed with DCM (1 mL) and the aqueous layer was acidified with concentrated HCl (250 μL) and extracted with DCM (2×1 mL). The DCM extracts were combined and concentrated in vacuo, and the resulting crude liquid was purified by reverse phase preparative HPLC to yield the title compound (2.9 mg). MS m/z [M+H]+ calc'd for C21H22ClNO5, 404.12. found 404.2.

Workup

  1. stirringthe mixture was stirred for an additional 1 hour
  2. washThe mixture was washed with DCM (1 mL)
  3. extractionextracted with DCM (2×1 mL)
  4. concentrationconcentrated in vacuo
  5. customthe resulting crude liquid was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-37e53ab9ddc0478b89c17fb115423ecb
Source dataset
uspto-grants-2016_08
Patent number
US09428457B2

Reaction notes

Loading…