Lithium Hydroxide → HCID 178438859, compound

HRID 523431Notes

Reaction equation

HRID 523431 reaction equation
[OH:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[O:4][N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O:45][C:46](=[O:68])[C@H:47]([CH2:66][OH:67])[CH2:48][C@H:49]([NH2:65])[C:50]([C:53]1[CH:58]=[CH:57][C:56]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)=[CH:55][CH:54]=1)([CH3:52])[CH3:51])C.[Li+].[OH-]>CN(C=O)C.CCO>[C:56]1([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:55]=[CH:54][C:53]([C:50]([CH3:52])([CH3:51])[C@@H:49]([NH:65][C:7]([C:5]2[O:4][N:3]=[C:2]([OH:1])[CH:6]=2)=[O:9])[CH2:48][C@@H:47]([CH2:66][OH:67])[C:46]([OH:68])=[O:45])=[CH:58][CH:57]=1

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68181182HCID 68181182, compoundHCID 178524642HCID 178524642, compound

Product 1

HCID 178438859HCID 178438859, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

3-Hydroxyisoxazole-5-carboxylic acid (15.8 mg, 122 μmol) was combined with HATU (46.6 mg, 122 μmol) in DMF (1.0 mL) and stirred for 5 minutes. DIPEA (53.3 μL, 0.306 mmol) was added, followed by (2S,4S)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-5-methylhexanoic acid ethyl ester (HCl salt; 40 mg, 0.1 mmol). The mixture was stirred at room temperature for 20 minutes. The reaction was quenched with water and extracted with EtOAc. The organic layer was concentrated and 1 M aqueous LiOH (1.0 mL, 1.0 mmol) and EtOH (2.0 mL) were added. The resulting mixture was stirred at room temperature for 2 hours. The reaction was quenched with AcOH and purified by preparative HPLC. The clean fractions were combined and lyophilized to yield the title compound (40 mg, 95% purity). MS m/z [M+H]+ calc'd for C24H26N2O6, 439.18. found 439.4.

Workup

  1. stirringThe mixture was stirred at room temperature for 20 minutes
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. concentrationThe organic layer was concentrated
  5. stirringThe resulting mixture was stirred at room temperature for 2 hours
  6. customThe reaction was quenched with AcOH
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-ef5813f8e3114bebbac7f8dc41149112
Source dataset
uspto-grants-2016_05
Patent number
US09334245B2

Reaction notes

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