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

HRID 1454207Notes

Reaction equation

HRID 1454207 reaction equation
C([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13](=[O:23])[NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH:12]=1)C(O)=O)(=O)C.CN([C:27]([O:31]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:57][O:58][C:59]1[CH:60]=[C:61]([CH:85]=[CH:86][CH:87]=1)[CH2:62][N:63]([CH2:71][C@@H:72]([OH:84])[C@@H:73]([NH2:83])[CH2:74][C:75]1[CH:80]=[C:79]([F:81])[CH:78]=[C:77]([F:82])[CH:76]=1)[C:64](=[O:70])[O:65][C:66]([CH3:69])([CH3:68])[CH3:67].CN(C=[O:92])C>C(OCC)(=O)C>[CH3:57][O:58][C:59]1[CH:60]=[C:61]([CH:85]=[CH:86][CH:87]=1)[CH2:62][N:63]([CH2:71][C@@H:72]([OH:84])[C@@H:73]([NH:83][C:27](=[O:31])[C:22]1[CH:17]=[C:15]([NH:14][C:13](=[O:23])[C:11]2[CH:12]=[CH:4][CH:5]=[CH:6][CH:10]=2)[CH:16]=[C:20]([C:19](=[O:92])[CH3:18])[CH:21]=1)[CH2:74][C:75]1[CH:76]=[C:77]([F:82])[CH:78]=[C:79]([F:81])[CH:80]=1)[C:64](=[O:70])[O:65][C:66]([CH3:69])([CH3:67])[CH3:68]

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 57529301(R)-3-acetyl-5-((1-phenylethyl)carbamoyl)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 (R)-3-acetyl-5-((1-phenylethyl)carbamoyl)benzoic acid (from step 3, 80.0 mg, 0.257 mmol), HATU (117 mg, 0.309 mmol) and Hunig's base (133 mg, 0.2 mL, 1.029 mmol) in DMF (2.0 mL) was stirred for 10 min and then tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate (112 mg, 0.257 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 (150 mg): HPLC retention time: 2.350 min (method A). MS (ESI) (M+H)+ 730.40.

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-84f97f3d02084f7fa32c4428ecb46eeb
Source dataset
uspto-grants-2009_01
Patent number
US07476764B2

Reaction notes

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