Dimethylformamide → tert-Butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(benzamido)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate

HRID 1454193Notes

Reaction equation

HRID 1454193 reaction equation
[C:1]([C:4]1[CH:5]=[C:6](C=C(C(=O)N(C)CCC)C=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].CN(C(ON1N=N[C:30]2[CH:31]=[CH:32][CH:33]=N[C:29]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N:46]([CH:50]([CH3:52])[CH3:51])[CH:47]([CH3:49])C.[CH3:53][O:54][C:55]1[CH:56]=[C:57]([CH:81]=[CH:82][CH:83]=1)[CH2:58][N:59]([CH2:67][C@@H:68]([OH:80])[C@@H:69]([NH2:79])[CH2:70][C:71]1[CH:76]=[C:75]([F:77])[CH:74]=[C:73]([F:78])[CH:72]=1)[C:60](=[O:66])[O:61][C:62]([CH3:65])([CH3:64])[CH3:63].CN(C=[O:88])C>C(OCC)(=O)C>[CH3:53][O:54][C:55]1[CH:56]=[C:57]([CH:81]=[CH:82][CH:83]=1)[CH2:58][N:59]([CH2:67][C@@H:68]([OH:80])[C@@H:69]([NH:79][C:7](=[O:9])[C:6]1[CH:51]=[C:50]([NH:46][C:47](=[O:88])[C:49]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:52]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1)[CH2:70][C:71]1[CH:72]=[C:73]([F:78])[CH:74]=[C:75]([F:77])[CH:76]=1)[C:60](=[O:66])[O:61][C:62]([CH3:65])([CH3:63])[CH3:64]

Participants

7

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 575292855-Acetyl-N-methyl-N-propyl-isophthalamic acidHCID 68827600tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate

Product 1

HCID 68827142tert-Butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(benzamido)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-acetyl-5-(methyl(propyl)carbamoyl)-benzoic acid (from step 3, 0.386 mmol), HATU (176 mg, 0.464 mmol) and Hunig's base (200 mg, 0.3 mL, 1.545 mmol) in DMF (4.0 mL) was stirred for 10 min and then tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate (168 mg, 0.386 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with H2O 3 times. The organic layer was dried over sodium sulfate and concentrated under vacuum. The crude product was purified by reverse phase prep HPLC to give the title compound (100 mg): HPLC retention time: 2.185 min (method A). MS (ESI) (M+H)+ 682.32.

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. washwashed with H2O 3 times
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product was purified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-e987beea6f2b461588d83d52c8b396e9
Source dataset
uspto-grants-2009_01
Patent number
US07476764B2

Reaction notes

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