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

HRID 14008

반응식

HRID 14008 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-bd18ce92150d48a3ad3fbecc0118dde7
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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