Dimethylformamide → HCID 178472577, compound

HRID 516456Notes

Reaction equation

HRID 516456 reaction equation
[OH:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]([OH:10])=O)[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.[CH2:40]([O:42][C:43](=[O:63])[C@H:44]([OH:62])[CH2:45][C@H:46]([NH2:61])[CH2:47][C:48]1[CH:53]=[CH:52][C:51]([C:54]2[CH:59]=[CH:58][CH:57]=[C:56]([Cl:60])[CH:55]=2)=[CH:50][CH:49]=1)[CH3:41].CCN(C(C)C)C(C)C>>[CH2:40]([O:42][C:43](=[O:63])[C@H:44]([OH:62])[CH2:45][C@H:46]([NH:61][C:8]([C:4]1[CH:3]=[C:2]([OH:1])[N:6]([CH3:7])[N:5]=1)=[O:10])[CH2:47][C:48]1[CH:53]=[CH:52][C:51]([C:54]2[CH:59]=[CH:58][CH:57]=[C:56]([Cl:60])[CH:55]=2)=[CH:50][CH:49]=1)[CH3:41]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 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 esterHCID 178481916HCID 178481916, compound

Product 1

HCID 178472577HCID 178472577, compoundYield 27.3%

Procedure

5-Hydroxy-1-methyl-1h-pyrazole-3-carboxylic acid (122 mg, 862 μmol) and HATU (361 mg, 949 μmol) were combined in DMF (1.0 mL, 13 mmol) and stirred for 10 minutes. (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (30.0 mg, 86 μmol) and DIPEA (165 μL, 949 μmol) were added, and the resulting mixture was stirred at room temperature overnight. 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 (11.1 mg). MS m/z [M+H]+ calc'd for C24H26ClN3O5, 472.16. found 472.2.

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  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-a1e22c1b7ca94f548df0a5cbf19ac39c
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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