Diisopropylethylamine → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methyl]benzamide

HRID 14100

Reaction equation

HRID 14100 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](O)=[O:7].C(N(C(C)C)CC)(C)C.CN(C([O:28][N:29]1[N:37]=[N:36][C:31]2[CH:32]=[CH:33][CH:34]=[N:35][C:30]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:47][C@@H:48]([CH2:62][C:63]1[CH:68]=[C:67]([F:69])[CH:66]=[C:65]([F:70])[CH:64]=1)[C@H:49]([OH:61])[CH2:50][NH:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[C:55]([CH2:59][CH3:60])[CH:54]=1>CN(C=O)C.C(Cl)Cl>[F:69][C:67]1[CH:68]=[C:63]([CH:64]=[C:65]([F:70])[CH:66]=1)[CH2:62][C@H:48]([NH:47][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][CH:11]=[C:3]([CH2:2][O:28][N:29]2[C:30]3=[N:35][CH:34]=[CH:33][CH:32]=[C:31]3[N:36]=[N:37]2)[CH:4]=1)[C@H:49]([OH:61])[CH2:50][NH:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[C:55]([CH2:59][CH3:60])[CH:54]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2456503-(Bromomethyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

Product 1

HCID 57512019N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methyl]benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To 3-(bromomethyl)benzoic acid (200 mg, 0.93 mmol) and diisopropylethylamine (566 μL, 3.26 mmol) in DMF (5 mL) is added HATU (424 mg, 1.12 mmol), and the reaction is stirred 5 min. To the reaction is added (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method in Example SP-272 (379 mg, 0.93 mmol), and the reaction stirred 30 min. The reaction mixture is diluted with methylene chloride, washed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine. The organic layer is then dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/chloroform) provides the title compound. ESI MS m/z 587.4 [M+H]+.

Workup

  1. stirringthe reaction stirred 30 min
  2. washwashed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine
  3. dry with materialThe organic layer is then dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 8% methanol/chloroform)

Sources & evidence

ORD record
ord-de8abf6422524d448c8ce2885ad39bc1
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

Loading…