Triethylamine → N'-{(1s,2r)-1-(3,5-Difluorobenzyl)-2-Hydroxy-3-[(3-Methoxybenzyl)amino]propyl}-5-Methyl-N,N-Dipropylisophthalamide

HRID 14008

Reaction equation

HRID 14008 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@@H:9]([CH2:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1.C(N(CC)CC)C.[CH3:39][C:40]1[CH:41]=[C:42]([C:49]([N:51]([CH2:55][CH2:56][CH3:57])[CH2:52][CH2:53][CH3:54])=[O:50])[CH:43]=[C:44]([CH:48]=1)[C:45](O)=[O:46].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[F:31][C:26]1[CH:25]=[C:24]([CH:29]=[C:28]([F:30])[CH:27]=1)[CH2:23][C@H:9]([NH:8][C:45](=[O:46])[C:44]1[CH:48]=[C:40]([CH3:39])[CH:41]=[C:42]([C:49]([N:51]([CH2:52][CH2:53][CH3:54])[CH2:55][CH2:56][CH3:57])=[O:50])[CH:43]=1)[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113913935-methyl-N,N-dipropylisophthalamic acidHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 9916309N'-{(1s,2r)-1-(3,5-Difluorobenzyl)-2-Hydroxy-3-[(3-Methoxybenzyl)amino]propyl}-5-Methyl-N,N-Dipropylisophthalamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol trifluoroacetate salt (VIII, EXAMPLE 5) is dissolved in anhydrous DMF (3 mL) and cooled to 0 degrees C. Triethylamine (500 microliter, 3.6 mmol) and 5-methyl-N,N-dipropylisophthalamic acid (156 mg, 0.59 mmol) are added with stirring. The mixture is warmed to 20-25 degrees C. briefly to allow for complete dissolution of the carboxylic acid, before recooling to 0 degrees C. 1-Hydroxybenzotriazole (157 mg, 1.2 mmol) is added with stirring, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (229 mg, 1.2 mmol). The resulting mixture is stirred at 0 degrees C. for 5 minutes, then warmed to 20-25 degrees C. for 15 hours. The reaction mixture is then quenched with aqueous citric acid (10%), and the mixture extracted three times with ethyl acetate. The combined organic extracts are washed with saturated sodium bicarbonate, saline, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound in crude form. This material is purified by flash chromatography (2-10% methanol/methylene chloride gradient elution) to give purified title compound, MS (ES) MH+=582.3.

Workup

  1. temperatureThe mixture is warmed to 20-25 degrees C
  2. custombefore recooling to 0 degrees C
  3. stirringwith stirring
  4. stirringThe resulting mixture is stirred at 0 degrees C
  5. temperaturewarmed to 20-25 degrees C
  6. waitfor 15 hours
  7. customThe reaction mixture is then quenched with aqueous citric acid (10%)
  8. extractionthe mixture extracted three times with ethyl acetate
  9. washThe combined organic extracts are washed with saturated sodium bicarbonate, saline
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bd18ce92150d48a3ad3fbecc0118dde7
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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