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Diisopropylethylamine → N1-butyl-N3-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N1-methyl-5-(1,3-oxazol-2-yl)isophthalamide

HRID 349089
Notes
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Reaction equation

HRID 349089 reaction equation
[CH2:1]([N:5]([CH3:22])[C:6]([C:8]1[CH:9]=[C:10]([CH:14]=[C:15]([C:17]2[O:18][CH:19]=[CH:20][N:21]=2)[CH:16]=1)[C:11]([OH:13])=O)=[O:7])[CH2:2][CH2:3][CH3:4].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>[CH2:1]([N:5]([CH3:22])[C:6](=[O:7])[C:8]1[CH:16]=[C:15]([C:17]2[O:18][CH:19]=[CH:20][N:21]=2)[CH:14]=[C:10]([C:11]([NH:58][C@@H:59]([CH2:73][C:74]2[CH:75]=[C:76]([F:81])[CH:77]=[C:78]([F:80])[CH:79]=2)[C@H:60]([OH:72])[CH2:61][NH:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:71])[CH:65]=2)=[O:13])[CH:9]=1)[CH2:2][CH2:3][CH3:4]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 210857323-{[Butyl(methyl)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 58802691
N1-butyl-N3-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N1-methyl-5-(1,3-oxazol-2-yl)isophthalamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

3-{[Butyl(methyl)amino]carbonyl}-5-(1,3-oxazol-2-yl)benzoic acid (237 mg, 0.78 mmol) is dissolved in DMF (5 mL), and diisopropylethylamine (546 μL, 3.1 mmol), HATU (358 mg, 0.94 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 (319 mg, 0.78 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-80333d6003c2401ba5a3dba980a15dd1
Source dataset
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07176242B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes