Diisopropylethylamine → [(2R,3S)-3-{3-Acetyl-5-[1-(4-fluoro-phenyl)-ethylcarbamoyl]-benzoyl-amino}-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-methoxy-benzyl)-carbamic acid tert-butyl ester

HRID 1454212Notes

Reaction equation

HRID 1454212 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13](=[O:24])[NH:14][CH:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH3:16])[CH:12]=1)[C:7](O)=[O:8])(=[O:3])[CH3:2].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.[CH3:58][O:59][C:60]1[CH:61]=[C:62]([CH:86]=[CH:87][CH:88]=1)[CH2:63][N:64]([CH2:72][C@@H:73]([OH:85])[C@@H:74]([NH2:84])[CH2:75][C:76]1[CH:81]=[C:80]([F:82])[CH:79]=[C:78]([F:83])[CH:77]=1)[C:65](=[O:71])[O:66][C:67]([CH3:70])([CH3:69])[CH3:68]>CN(C=O)C.C(OCC)(=O)C>[C:67]([O:66][C:65](=[O:71])[N:64]([CH2:72][C@@H:73]([OH:85])[C@@H:74]([NH:84][C:7](=[O:8])[C:6]1[CH:10]=[C:11]([C:13](=[O:24])[NH:14][CH:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH3:16])[CH:12]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1)[CH2:75][C:76]1[CH:77]=[C:78]([F:83])[CH:79]=[C:80]([F:82])[CH:81]=1)[CH2:63][C:62]1[CH:86]=[CH:87][CH:88]=[C:60]([O:59][CH3:58])[CH:61]=1)([CH3:70])([CH3:68])[CH3:69]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 575293003-Acetyl-5-((1-(4-fluorophenyl)ethyl)carbamoyl)benzoic acidHCID 68827600tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate

Product 1

HCID 57529278[(2R,3S)-3-{3-Acetyl-5-[1-(4-fluoro-phenyl)-ethylcarbamoyl]-benzoyl-amino}-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-methoxy-benzyl)-carbamic acid tert-butyl esterYield 78.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-acetyl-5-((1-(4-fluorophenyl)ethyl)carbamoyl)benzoic acid (from step 3, 85.0 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: 2.265 min (method A). MS (ESI) (M+H)+ 748.47.

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-b829ad3c12d04990af1eebb097cff4b3
Source dataset
uspto-grants-2009_01
Patent number
US07476764B2

Reaction notes

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