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

HRID 1454187Notes

Reaction equation

HRID 1454187 reaction equation
[C:1]([C:4]1[CH:5]=[C:6](C=C(C(=O)N(CCC)CCC)C=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].CN(C(ON1N=N[C:32]2[CH:33]=[CH:34][CH:35]=N[C:31]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N:48]([CH:52]([CH3:54])[CH3:53])[CH:49]([CH3:51])C.[CH3:55][O:56][C:57]1[CH:58]=[C:59]([CH:83]=[CH:84][CH:85]=1)[CH2:60][N:61]([CH2:69][C@@H:70]([OH:82])[C@@H:71]([NH2:81])[CH2:72][C:73]1[CH:78]=[C:77]([F:79])[CH:76]=[C:75]([F:80])[CH:74]=1)[C:62](=[O:68])[O:63][C:64]([CH3:67])([CH3:66])[CH3:65].CN(C=[O:90])C>C(OCC)(=O)C>[CH3:55][O:56][C:57]1[CH:58]=[C:59]([CH:83]=[CH:84][CH:85]=1)[CH2:60][N:61]([CH2:69][C@@H:70]([OH:82])[C@@H:71]([NH:81][C:7](=[O:9])[C:6]1[CH:53]=[C:52]([NH:48][C:49](=[O:90])[C:51]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:54]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1)[CH2:72][C:73]1[CH:74]=[C:75]([F:80])[CH:76]=[C:77]([F:79])[CH:78]=1)[C:62](=[O:68])[O:63][C:64]([CH3:67])([CH3:65])[CH3:66]

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 575292993-Acetyl-5-(dipropylcarbamoyl)benzoic 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-(dipropylcarbamoyl)benzoic acid (95 mg, 0.326 mmol), HATU (149 mg, 0.392 mmol) and Hunig's base (168.8 mg, 0.2 mL, 1.306 mmol) in DMF (2.9 mL) was stirred for 10 min and then tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate (142 mg, 0.326 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 to give the title compound (220 mg) which was ready for next step without further purification: 1H NMR (CD3OD, 500 MHz) δ ppm 0.71 (3H, m), 1.02 (3H, m), 1.48-1.55 (11H, m), 1.74-1.76 (2H, m), 2.66 (2H, m), 2.87 (1H, m), 3.11-3.17 (3H, m), 3.33 (1H, m), 3.50 (2H, m), 3.76 (4H, m), 3.98 (1H, m), 4.32 (1H, m), 4.42-4.45 (1H, m), 4.68-4.82 (2H, m), 6.70-6.74 (1H, m), 6.80 (3H, m), 6.90 (2H, m), 7.22 (1H, m), 7.51-7.87 (1H, m), 8.07 (1H, m), 8.36-8.56 (1H, m). HPLC retention time: 2.195 min (method B). MS (ESI) (M+H)+ 710.31.

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

Sources & evidence

ORD record
ord-da5eb30a5130497fbaf63aa3480a5aef
Source dataset
uspto-grants-2009_01
Patent number
US07476764B2

Reaction notes

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