Hydrochloric Acid → n-{(1s,2r)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(1,3-oxazol-2-yl)benzamide hydrochloride

HRID 349101Notes

Reaction equation

HRID 349101 reaction equation
CN([C:4]([O:8]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]1[CH:26]=[CH:27][C:28]2N(O)N=N[C:29]=2[CH:30]=1.[CH:35](N(C(C)C)CC)(C)C.[C:44]1([NH2:55])[C:49](F)=C(F)C(F)=C(N)C=1F.[ClH:56].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.Cl.[CH2:83]([O:85]CC)C>C(Cl)Cl.CO>[ClH:56].[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:4](=[O:8])[C:30]1[CH:29]=[C:28]([C:83]2[O:85][CH:49]=[CH:44][N:55]=2)[CH:27]=[C:26]([CH3:35])[CH:25]=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

10

Reactant 7

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 68607788n-{(1s,2r)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(1,3-oxazol-2-yl)benzamide hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of the acid from step 6 (358 mg, 1.8 mmol), HATU (1.0 g, 2.6 mmol), HOBt (357 mg, 2.6 mmol), and diisopropylethylamine (500 μL, 2.6 mmol) was stirred in methylene chloride (2.0 mL) for 15 min. A solution of dihydrochloride of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (718 mg, 1.8 mmol) and diisopropylethylamine (500 μL, 2.6 mmol) in methylene chloride (2.0 mL) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided a clear solid. The solid was dissolved in methanol (2 mL), and treated with hydrochloric acid (0.5 mL of a 1.0 M solution in diethyl ether, 0.5 mmol). The resulting precipitate was collected by filtration to provide the title compound (250 mg): mp 105–107° C.; APCI MS m/z 520 [M+H]+.

Workup

  1. washwashed with 1 N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)
  6. customprovided a clear solid
  7. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-64464c1e04f742e6abc25a1896765d6b
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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