Diisopropylethylamine → HCID 178448383, compound

HRID 523425Notes

Reaction equation

HRID 523425 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[N:2]1.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.C(OC([NH:52][C@@H:53]([CH:81]([CH3:83])[CH3:82])[C:54]([O:56][CH2:57][O:58][C:59](=[O:80])[C@@:60]([CH2:78][OH:79])([CH3:77])[CH2:61][C@H:62]([NH2:76])[CH2:63][C:64]1[CH:69]=[CH:68][C:67]([C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)=[CH:66][CH:65]=1)=[O:55])=O)C1C=CC=CC=1>CN(C=O)C>[NH2:52][C@@H:53]([CH:81]([CH3:83])[CH3:82])[C:54]([O:56][CH2:57][O:58][C:59](=[O:80])[C@@:60]([CH2:78][OH:79])([CH3:77])[CH2:61][C@H:62]([NH:76][C:6]([C:4]1[NH:3][N:2]=[N:1][CH:5]=1)=[O:8])[CH2:63][C:64]1[CH:65]=[CH:66][C:67]([C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)=[CH:68][CH:69]=1)=[O:55]

Participants

6

Reactant 4

HCID 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 86669863HCID 86669863, compound

Product 1

HCID 178448383HCID 178448383, compoundYield 29.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

1,2,3-Triazole-4-carboxylic acid (18 mg, 156 μmol), DIPEA (81.6 μL, 468 μmol) and HATU (59.3 mg, 156 μmol) were combined in DMF (0.2 mL) and stirred for 5 minutes at room temperature. This was then combined with (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-benzyloxycarbonylamino-3-methyl-butyryloxymethyl ester (90 mg, 160 μmol) dissolved in DMF (1 mL). The resulting mixture was stirred for 20 minutes and the solvent was evaporated. The remaining solid was dissolved in degassed 4.4% formic acid-methanol (5 mL) in a flask containing palladium black (˜100 mg) under nitrogen. The mixture was continuously stirred at room temperature. The mixture was filtered and washed with MeOH. The solvent was evaporated and the product purified by preparative HPLC to yield the title compound (25 mg; purity 95%). MS m/z [M+H]+ calc'd for C28H35N5O6, 538.26. found 538.4.

Workup

  1. stirringThe resulting mixture was stirred for 20 minutes
  2. customthe solvent was evaporated
  3. dissolutionThe remaining solid was dissolved in degassed 4.4% formic acid-methanol (5 mL) in a flask
  4. additioncontaining palladium black (˜100 mg) under nitrogen
  5. stirringThe mixture was continuously stirred at room temperature
  6. filtrationThe mixture was filtered
  7. washwashed with MeOH
  8. customThe solvent was evaporated
  9. customthe product purified by preparative HPLC

Sources & evidence

ORD record
ord-60a221b1dac743a18d2aacd23dc95d70
Source dataset
uspto-grants-2016_05
Patent number
US09334245B2

Reaction notes

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