Methanol → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic Acid

HRID 516465Notes

Reaction equation

HRID 516465 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:12]=[C:11]([C:13]([OH:15])=O)[O:10][N:9]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.C([O:47][C:48](=[O:68])[C@H:49]([OH:67])[CH2:50][C@H:51]([NH2:66])[CH2:52][C:53]1[CH:58]=[CH:57][C:56]([C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([Cl:65])[CH:60]=2)=[CH:55][CH:54]=1)C.CCN(C(C)C)C(C)C.CO.O>>[Cl:65][C:61]1[CH:60]=[C:59]([C:56]2[CH:55]=[CH:54][C:53]([CH2:52][C@@H:51]([NH:66][C:13]([C:11]3[O:10][N:9]=[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])[CH:12]=3)=[O:15])[CH2:50][C@@H:49]([OH:67])[C:48]([OH:68])=[O:47])=[CH:58][CH:57]=2)[CH:64]=[CH:63][CH:62]=1

Participants

8

Reactant 7

HCID 887MethanolHCID 962WaterHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 31602553-(2-Fluorophenyl)-1,2-oxazole-5-carboxylic acidHCID 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 86705154(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic AcidYield 57.9%

Procedure

To a mixture of 3-(2-fluorophenyl)isoxazole-5-carboxylic acid (14.3 mg, 69 μmol) and HATU (26.2 mg, 69 μmol) in DMF (0.5 mL, 6 mmol) at room temperature, was added (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (20.0 mg, 58 μmol) and DIPEA (20.0 μL, 115 μmol). The mixture was stirred at room temperature overnight. MeOH (2.0 mL, 49 mmol), water (1.0 mL, 56 mmol), and LiOH monohydrate (9.7 mg, 230 μmol) was added, and the resulting mixture was stirred at room temperature for 1 hour. The resulting solids were filtered and rinsed with MeCN and water to yield the title compound (17.1 mg). MS m/z [M+H]+ calc'd for C27H22ClFN2O5, 509.12. found 509.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 1 hour
  2. filtrationThe resulting solids were filtered
  3. washrinsed with MeCN and water

Sources & evidence

ORD record
ord-06eda4858ec542c9a53f2c19c45bc186
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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