Diisopropylethylamine → N1-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-ethyl-5-(1,3-oxazol-2-yl)-N3-propylisophthalamide

HRID 14304Notes

Reaction equation

HRID 14304 reaction equation
[CH2:1]([N:3]([CH2:20][CH2:21][CH3:22])[C:4]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([C:15]2[O:16][CH:17]=[CH:18][N:19]=2)[CH:14]=1)[C:9](O)=[O:10])=[O:5])[CH3:2].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:58][C@@H:59]([CH2:73][C:74]1[CH:79]=[C:78]([F:80])[CH:77]=[C:76]([F:81])[CH:75]=1)[C@H:60]([OH:72])[CH2:61][NH:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:71])[CH:65]=1>CN(C=O)C.C(Cl)(Cl)Cl>[F:81][C:76]1[CH:75]=[C:74]([CH:79]=[C:78]([F:80])[CH:77]=1)[CH2:73][C@H:59]([NH:58][C:9](=[O:10])[C:8]1[CH:12]=[C:13]([C:15]2[O:16][CH:17]=[CH:18][N:19]=2)[CH:14]=[C:6]([C:4]([N:3]([CH2:1][CH3:2])[CH2:20][CH2:21][CH3:22])=[O:5])[CH:7]=1)[C@H:60]([OH:72])[CH2:61][NH:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:71])[CH:65]=1

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 210858313-{[Ethyl(propyl)amino]carbonyl}-5-(1,3-oxazol-2-yl)benzoic AcidHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

Product 1

HCID 58802578N1-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3-ethyl-5-(1,3-oxazol-2-yl)-N3-propylisophthalamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

3-{[Ethyl(propyl)amino]carbonyl}-5-(1,3-oxazol-2-yl)benzoic acid (290 mg, 0.96 mmol) is dissolved in DMF (5 mL), and diisopropylethylamine (668 μL, 3.8 mmol), HATU (438 mg, 1.15 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method of EXAMPLE SP-272 (391 mg, 0.96 mmol) are added. The reaction stirred at room temperature 5 h. The reaction mixture is diluted with chloroform, washed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 9% methanol/methylene chloride) provides the title compound. ESI MS m/z 619;3 [M+H]+.

Workup

  1. additionare added
  2. washwashed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, saturated sodium chloride
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 9% methanol/methylene chloride)

Sources & evidence

ORD record
ord-dac689f44d6d47418c28ed32126541d3
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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