Hydrochloric Acid → HCID 178471713, compound

HRID 535166Notes

Reaction equation

HRID 535166 reaction equation
N1C=C(C(O)=[O:7])N=N1.CN(C(O[N:17]1[N:25]=[N:24][C:19]2[CH:20]=CC=N[C:18]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN([CH:39]([CH3:41])C)C(C)C.[C:42]1([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[CH:47]=[CH:46][C:45]([CH2:48][C@@H:49]([NH:58]C(OC(C)(C)C)=O)[CH2:50][C@:51]([CH2:56][OH:57])([CH3:55])[C:52]([OH:54])=[O:53])=[CH:44][CH:43]=1.Cl>CN(C=O)C.CCO.O1CCOCC1>[CH2:39]([O:54][C:52](=[O:53])[C@@:51]([CH2:56][OH:57])([CH3:55])[CH2:50][C@H:49]([NH:58][C:20]([C:19]1[NH:24][N:25]=[N:17][CH:18]=1)=[O:7])[CH2:48][C:45]1[CH:46]=[CH:47][C:42]([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)=[CH:43][CH:44]=1)[CH3:41]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 1401204-Carboxy-1,2,3-triazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid

Product 1

HCID 178471713HCID 178471713, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

1,2,3-Triazole-4-carboxylic acid (11.5 mg, 102 μmol, 1.2 eq.) and HATU (38.6 mg, 102 μmol, 1.2 eq.) were dissolved in DMF (0.9 mL) and stirred at room temperature for 5 minutes. DIPEA (29.5 μL, 2.0 eq.) was added to yield the activated acid. (2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (35 mg, 85 μmol, 1.0 eq.) was dissolved in EtOH and 4 M of HCl in dioxane (423 μL) was added. The mixture was heated to 60° C. overnight, then concentrated to dryness and purified by reverse phase chromatography (5-60% MeCN in water over 18 minutes. The clean fractions were combined and dried under vacuum to dryness, then combined with the activated acid. After 20 minutes, the reaction was quenched with water and the product was dried under vacuum and purified by preparative HPLC to yield the title compound (4 mg, >95% purity. MS m/z [M+H]+ calc'd for C24H28N4O4, 437.21. found 437.3.

Workup

  1. customto yield the activated acid
  2. temperatureThe mixture was heated to 60° C. overnight
  3. concentrationconcentrated to dryness
  4. custompurified by reverse phase chromatography (5-60% MeCN in water over 18 minutes
  5. customdried under vacuum to dryness
  6. waitAfter 20 minutes
  7. customthe reaction was quenched with water
  8. customthe product was dried under vacuum
  9. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-e0c57e16cd614bc5ac56c2366bdf9f93
Source dataset
uspto-grants-2014_10
Patent number
US08853427B2

Reaction notes

Loading…