Hydrochloric Acid → HCID 68610793, compound

HRID 14206Notes

Reaction equation

HRID 14206 reaction equation
C(OC([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]([OH:20])=O)=[CH:15][CH:16]=2)[N:11]([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:10][CH2:9]1)=O)(C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[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.[ClH:82]>C(Cl)Cl.CO>[ClH:82].[CH2:21]([N:11]1[C:12]2[C:17](=[CH:16][CH:15]=[C:14]([C:18]([NH:58][C@@H:59]([CH2:73][C:74]3[CH:75]=[C:76]([F:81])[CH:77]=[C:78]([F:80])[CH:79]=3)[C@H:60]([OH:72])[CH2:61][NH:62][CH2:63][C:64]3[CH:69]=[CH:68][CH:67]=[C:66]([CH2:70][CH3:71])[CH:65]=3)=[O:20])[CH:13]=2)[NH:8][CH2:9][CH2:10]1)[CH2:22][CH2:23][CH3:24]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210853571-(Tert-butoxycarbonyl)-4-butyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 68610793HCID 68610793, compoundYield 21.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 1-(tert-butoxycarbonyl)-4-butyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (120 mg), HBTU (204 g), and diisopropylethylamine (100 μL) was stirred in methylene chloride (2.0 mL) for 15 min. A solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (146 mg) and diisopropylethylamine (100 μL) in methylene chloride (2.0 mL) was added and the mixture was stirred overnight. The mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (10 mL), saturated sodium bicarbonate (10 mL), and brine. The organic layer was then 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 (1 mL), and treated with hydrochloric acid (0.5 mL, 1.0 M diethyl ether, 0.5 mmol). The resulting precipitate was collected by filtration to provide 45 mg of the title compound: ESI MS m/z 551 [M+H]+.

Workup

  1. washwashed with 1 N hydrochloric acid (10 mL), saturated sodium bicarbonate (10 mL), and brine
  2. dry with materialThe organic layer was then dried (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-ccaee225b88f40dca0e4398d283de183
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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