Hydrochloric Acid → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2-hydroxyethyl)(methyl)amino]methyl}-5-methylbenzamide Dihydrochloride

HRID 14151Notes

Reaction equation

HRID 14151 reaction equation
[OH:1][CH2:2][CH2:3][N:4]([CH2:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([CH3:16])[CH:15]=1)[C:10]([OH:12])=O)[CH3:5].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.[NH2:60][C@@H:61]([CH2:75][C:76]1[CH:81]=[C:80]([F:82])[CH:79]=[C:78]([F:83])[CH:77]=1)[C@H:62]([OH:74])[CH2:63][NH:64][CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[C:68]([CH2:72][CH3:73])[CH:67]=1.[ClH:84]>C(Cl)Cl.CO.O1CCOCC1.C(OCC)C>[ClH:84].[ClH:84].[F:82][C:80]1[CH:81]=[C:76]([CH:77]=[C:78]([F:83])[CH:79]=1)[CH2:75][C@H:61]([NH:60][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([CH3:16])[CH:15]=[C:7]([CH2:6][N:4]([CH2:3][CH2:2][OH:1])[CH3:5])[CH:8]=1)[C@H:62]([OH:74])[CH2:63][NH:64][CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[C:68]([CH2:72][CH3:73])[CH:67]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21085670HCID 21085670, compoundHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 68608342N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2-hydroxyethyl)(methyl)amino]methyl}-5-methylbenzamide Dihydrochloride

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 3-{[(2-hydroxyethyl)(methyl)amino]methyl}-5-methylbenzoic acid (140 mg, 0.56 mmol) in methylene chloride (3 mL) is added HBTU (318 mg, 0.84 mmol), HOBt (114 mg, 0.84 mmol), and N,N -diisopropylethylamine (0.284 mL, 1.68 mmol), followed by (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (228 mg, 0.56 mmol). The reaction mixture is stirred for 24 h at room temperature, diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (10% methanol/chloroform) affords a clear oil, which is dissolved in methanol (2 mL). To this is added hydrochloric acid (5 mL of a 4 N solution in dioxane, 20 mmol), and the reaction mixture is stirred for 1 h at room temperature. The reaction mixture is diluted with ethyl ether (10 mL) The precipitate that is formed is collected by filtration to provide the title compound. ESI MS m/z 540.4 [M+H]+.

Workup

  1. washwashed with water, and saturated sodium bicarbonate
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (10% methanol/chloroform)
  6. customaffords a clear oil, which
  7. stirringis stirred for 1 h at room temperature
  8. customis formed
  9. filtrationis collected by filtration

Sources & evidence

ORD record
ord-2a3379bb0d8d44b6a0f9c602ae2aa9f3
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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