Diisopropylethylamine → N1-((1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N3,N3-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide Dihydrochloride

HRID 349095Notes

Reaction equation

HRID 349095 reaction equation
[CH2:1]([N:4]([CH2:21][CH2:22][CH3:23])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:15]=1)[C:10](O)=[O:11])=[O:6])[CH2:2][CH3:3].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.[ClH:57].Cl.[NH2:59][C@@H:60]([CH2:76][C:77]1[CH:82]=[C:81]([F:83])[CH:80]=[C:79]([F:84])[CH:78]=1)[C@H:61]([OH:75])[CH2:62][NH:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[C:67]([C:71]([F:74])([F:73])[F:72])[CH:66]=1>CN(C=O)C.C(Cl)(Cl)Cl>[ClH:57].[ClH:57].[F:84][C:79]1[CH:78]=[C:77]([CH:82]=[C:81]([F:83])[CH:80]=1)[CH2:76][C@H:60]([NH:59][C:10](=[O:11])[C:9]1[CH:13]=[C:14]([C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:21][CH2:22][CH3:23])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)[C@H:61]([OH:75])[CH2:62][NH:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[C:67]([C:71]([F:72])([F:73])[F:74])[CH:66]=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 210857833-[(Dipropylamino)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 86594201N1-((1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-N3,N3-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide Dihydrochloride

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

3-[(Dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoic acid is dissolved in DMF (10 mL), and diisopropylethylamine (364 μL, 2.1 mmol), HATU (237 mg, 0.62 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol dihydrochloride prepared by the method of EXAMPLE SP-311 (250 mg, 0.52 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 689.3 [M+H]+.

Workup

  1. additionare added
  2. washwashed with water, 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, 8% methanol/methylene chloride)

Sources & evidence

ORD record
ord-2a0cd92a042e4037852028cf9647c972
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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