Hydrochloric Acid → HCID 178523852, compound

HRID 535162Notes

Reaction equation

HRID 535162 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:7]([OH:9])=O)[NH:5][N:6]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O:36][C:37](=[O:64])[C@H:38]([CH2:62][OH:63])[CH2:39][C@H:40]([NH:54]C(OC(C)(C)C)=O)[CH2:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[CH:44][CH:43]=1)C.Cl.O1CCOCC1>CN(C=O)C.CC#N>[C:45]1([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:44]=[CH:43][C:42]([CH2:41][C@@H:40]([NH:54][C:7]([C:4]2[NH:5][N:6]=[C:2]([Cl:1])[N:3]=2)=[O:9])[CH2:39][C@@H:38]([CH2:62][OH:63])[C:37]([OH:64])=[O:36])=[CH:47][CH:46]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68181146HCID 68181146, compoundHCID 178524894HCID 178524894, compound

Product 1

HCID 178523852HCID 178523852, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

5-Chloro-2H-1,2,4-triazole-3-carboxylic acid (51.8 mg, 351 μmol, 1.5 eq.) and HATU (133 mg, 351 μmol, 1.5 eq.) were dissolved in DMF (3.0 mL), and the resulting mixture was stirred for 5 minutes to yield the activated acid. (2S,4S)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-pentanoic acid ethyl ester (100 mg, 234 μmol, 1.0 eq.) was dissolved in MeCN (2 mL) followed by the addition of 4 M of HCl in dioxane (0.5 mL, 2.0 mmol). The mixture was stirred at room temperature for 2 hours, then concentrated to dryness. The activated acid was added and the resulting mixture was stirred for 2 minutes, followed by the addition of DIPEA (81.5 μL). The mixture was stirred at room temperature for 1 hour. The reaction was quenched with water, and the solvent removed under vacuum. The dried solid was dissolved in EtOH (2.0 mL) followed by the addition of 1.0 M of LiOH in water (2.0 mL). The mixture was stirred at room temperature for 3 hours, and the reaction was quenched with AcOH. The solvent was removed under vacuum, the residue was dissolved in AcOH/MeCN and purified by preparative HPLC. The clean fractions were combined and lyophilized to yield the title compound (61 mg, 95% purity). MS m/z [M+H]+ calc'd for C21H21ClN4O4, 429.13. found 429.4.

Workup

  1. customto yield the activated acid
  2. stirringThe mixture was stirred at room temperature for 2 hours
  3. concentrationconcentrated to dryness
  4. additionThe activated acid was added
  5. stirringthe resulting mixture was stirred for 2 minutes
  6. additionfollowed by the addition of DIPEA (81.5 μL)
  7. stirringThe mixture was stirred at room temperature for 1 hour
  8. customThe reaction was quenched with water
  9. customthe solvent removed under vacuum
  10. dissolutionThe dried solid was dissolved in EtOH (2.0 mL)
  11. additionfollowed by the addition of 1.0 M of LiOH in water (2.0 mL)
  12. stirringThe mixture was stirred at room temperature for 3 hours
  13. customthe reaction was quenched with AcOH
  14. customThe solvent was removed under vacuum
  15. dissolutionthe residue was dissolved in AcOH/MeCN
  16. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-33f1a330045548028024c8e7b703e091
Source dataset
uspto-grants-2014_10
Patent number
US08853427B2

Reaction notes

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