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

HRID 14307Notes

Reaction equation

HRID 14307 reaction equation
[CH2:1]([N:5]([CH3:22])[C:6]([C:8]1[CH:9]=[C:10]([CH:14]=[C:15]([C:17]2[S:18][CH:19]=[CH:20][N:21]=2)[CH:16]=1)[C:11]([OH:13])=O)=[O:7])[CH2:2][CH2:3][CH3:4].[CH:23](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]([CH2:75][C:76]1[CH:81]=[C:80]([F:82])[CH:79]=[C:78]([F:83])[CH:77]=1)[C@H:60]([OH:74])[CH2:61][NH:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[C:66]([C:70](F)(F)F)[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[S:18][CH:19]=[CH:20][N:21]=2)[CH:14]=[C:10]([C:11]([NH:58][C@@H:59]([CH2:75][C:76]2[CH:81]=[C:80]([F:82])[CH:79]=[C:78]([F:83])[CH:77]=2)[C@H:60]([OH:74])[CH2:61][NH:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:23])[CH:65]=2)=[O:13])[CH:9]=1)[CH2:2][CH2:3][CH3:4]

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 210857333-{[Butyl(methyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoic acidHCID 57487373(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol dihydrochloride

Product 1

HCID 10282843N1-Butyl-N3-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N1-methyl-5-(1,3-thiazol-2-yl)isophthalamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

3-{[Butyl(methyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoic acid (125 mg, 0.39 mmol) is dissolved in DMF (3 mL), and diisopropylethylamine (271 μL, 1.6 mmol), HATU (178 mg, 0.47 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol dihydrochloride (176 mg, 0.43 mmol) are added. The reaction stirred at room temperature 4 h. The reaction mixture is diluted with chloroform, washed with water, saturated sodium bicarbonate, saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/methylene chloride) provides the title compound as the free base. The residue is dissolved in diethyl ether (3 mL) and 1N hydrochloric acid in diethyl ether (2 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 635.3 [M+H]+.

Workup

  1. washwashed with water, saturated sodium bicarbonate, saturated sodium chloride
  2. dry with materialdried (sodium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 8% methanol/methylene chloride)

Sources & evidence

ORD record
ord-b9c2a0c919964a5ba723c66a3dbc2f60
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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