Dimethylformamide → (2R,3R)-2-hydroxy-3-(1-((2'-(N-(methoxycarbonyl)-sulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-4-phenylbutanoic Acid

HRID 1803785Notes

Reaction equation

HRID 1803785 reaction equation
[CH3:1][O:2][C:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[CH:20]=[CH:19][C:18]([CH2:21][N:22]2[C:26]([CH2:27][CH2:28][CH3:29])=[CH:25][C:24]([C:30]([OH:32])=O)=[N:23]2)=[CH:17][CH:16]=1)(=[O:8])=[O:7])=[O:4].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.[NH2:71][C@H:72]([CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)[C@@H:73]([OH:77])[C:74]([OH:76])=[O:75]>>[OH:77][C@H:73]([C@H:72]([NH:71][C:30]([C:24]1[CH:25]=[C:26]([CH2:27][CH2:28][CH3:29])[N:22]([CH2:21][C:18]2[CH:19]=[CH:20][C:15]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[S:6](=[O:8])(=[O:7])[NH:5][C:3]([O:2][CH3:1])=[O:4])=[CH:16][CH:17]=2)[N:23]=1)=[O:32])[CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)[C:74]([OH:76])=[O:75]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 638739(2R,3R)-3-amino-2-hydroxy-4-phenylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581029031-((2'-(N-(methoxycarbonyl)sulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 58102914(2R,3R)-2-hydroxy-3-(1-((2'-(N-(methoxycarbonyl)-sulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-4-phenylbutanoic AcidYield 95%

Procedure

A solution of 1-((2′-(N-(methoxycarbonyl)sulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxylic acid (40.2 mg, 87.8 μmol), DIPEA (91.8 μL, 527 μmol) and HATU (33.4 mg, 87.8 μmol) in DMF (0.4 mL, 4 mmol) was stirred to pre-activate the acid. After 1 minute, (2R,3R)-3-amino-2-hydroxy-4-phenylbutyric acid (17.1 mg, 87.8 μmol) was added, and the mixture was stirred for 10 minutes. The reaction was quenched by adding 1 N HCl and extracted with DCM. The organic layer was added to AcOH (1 mL) and evaporated in vacuo. The material was then purified by preparative HPLC to yield the title compound (10 mg, 95% purity). MS m/z: [M+H]+ calcd for C32H34N4O8S, 635.21; found 635.20.

Workup

  1. customThe reaction was quenched
  2. additionby adding 1 N HCl
  3. extractionextracted with DCM
  4. additionThe organic layer was added to AcOH (1 mL)
  5. customevaporated in vacuo
  6. customThe material was then purified by preparative HPLC

Sources & evidence

ORD record
ord-4cf8eb3293314ea68c011afd81389e1e
Source dataset
uspto-grants-2013_01
Patent number
US08350027B2

Reaction notes

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