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

HRID 1869715Notes

Reaction equation

HRID 1869715 reaction equation
[NH2:1][C@@H:2]([CH2:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=1)[C@H:3]([OH:15])[CH2:4][NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=1.C(N(CC)CC)C.[CH3:32][C:33]1[CH:34]=[C:35]([C:42]([N:44]([CH2:48][CH2:49][CH3:50])[CH2:45][CH2:46][CH3:47])=[O:43])[CH:36]=[C:37]([CH:41]=1)[C:38](O)=[O:39].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[F:24][C:19]1[CH:18]=[C:17]([CH:22]=[C:21]([F:23])[CH:20]=1)[CH2:16][C@H:2]([NH:1][C:38](=[O:39])[C:37]1[CH:41]=[C:33]([CH3:32])[CH:34]=[C:35]([C:42]([N:44]([CH2:45][CH2:46][CH3:47])[CH2:48][CH2:49][CH3:50])=[O:43])[CH:36]=1)[C@H:3]([OH:15])[CH2:4][NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11371095(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanolHCID 113913935-methyl-N,N-dipropylisophthalamic acid

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

Procedure

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol (VIII, EXAMPLE 6) is dissolved in anhydrous DMF (3 mL) and cooled to 0°. Triethylamine (500 μL, 3.6 mmol) and 5-methyl-N, N-dipropylisophthalamic acid (IX, 156 mg, 0.59 mmol) are added with stirring. The mixture is warmed to 20-25° briefly to allow for complete dissolution of the carboxylic acid, before recooling to 00. 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° for 5 min, then warmed to 20-25° for 15 hr. The 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. temperaturecooled to 0°
  2. temperatureThe mixture is warmed to 20-25° briefly
  3. stirringwith stirring
  4. stirringThe resulting mixture is stirred at 0° for 5 min
  5. temperaturewarmed to 20-25° for 15 hr
  6. customThe mixture is then quenched with aqueous citric acid (10%)
  7. extractionthe mixture extracted three times with ethyl acetate
  8. washThe combined organic extracts are washed with saturated sodium bicarbonate, saline
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7d2f4b6c595445b2a7b27842921781e8
Source dataset
uspto-grants-2009_12
Patent number
US07638646B2

Reaction notes

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