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Hydrochloric Acid → (+/-)-3-(6-(1-(2,6-Dimethyl-4'-(trifluoromethyl)biphenyl-4-ylamino)-3-methylbutyl)nicotinamido)propanoic acid

HRID 2406940
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HRID 2406940 반응식
[CH3:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]([C:14]2[CH:28]=[CH:27][C:17]([C:18]([NH:20][CH2:21][CH2:22][C:23]([O:25]C)=[O:24])=[O:19])=[CH:16][N:15]=2)[CH2:10][CH:11]([CH3:13])[CH3:12])[CH:5]=[C:4]([CH3:29])[C:3]=1[C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1.[Li+].[OH-].Cl>O.O1CCCC1>[CH3:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]([C:14]2[CH:28]=[CH:27][C:17]([C:18]([NH:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:19])=[CH:16][N:15]=2)[CH2:10][CH:11]([CH3:13])[CH3:12])[CH:5]=[C:4]([CH3:29])[C:3]=1[C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1
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반응물 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 67981001Methyl 3-(6-(1-(2,6-dimethyl-4'-(trifluoromethyl)biphenyl-4-ylamino)-3-methylbutyl)nicotinamido)propanoate

생성물 1

HCID 57389840(+/-)-3-(6-(1-(2,6-Dimethyl-4'-(trifluoromethyl)biphenyl-4-ylamino)-3-methylbutyl)nicotinamido)propanoic acid수율 13%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 8028Tetrahydrofuran용매

실험 절차

Methyl 3-(6-(1-(2,6-dimethyl-4′-(trifluoromethyl) biphenyl-4-yl amino)-3-methylbutyl)nicotinamido)propanoate (400 mg, 0.74 mmol) was dissolved in H2O (3 mL) and tetrahydrofuran (3 mL). Then 1N LiOH (93.0 mg, 2.2 mmol) was added. The mixture was stirred at ambient temperature for 5 hours. The mixture was neutralized with 1N HCl and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by HPLC (column: Boston Analytics Symmetrix ODS-H 150×30 mm, 5 μm; modifier: formic acid 0.225%; gradient: 10 to 80% MeCN in water) gave (+/−)-3-(6-(1-(2,6-dimethyl-4′-(trifluoromethyl)biphenyl-4-ylamino)-3-methylbutyl)nicotinamido)propanoic acid (50.7 mg, 13%) as a yellow solid. 1H NMR (400 MHz, CD3CN, δ): 8.85 (s, 1H), 8.02 (m, 1H), 7.64 (d, 2H), 7.46 (d, 1H), 7.22 (d, 3H), 6.32 (s, 2H), 4.59 (m, 1H), 3.54 (m, 2H), 2.55 (m, 2H), 1.93 (m, 6H), 1.78 (s, 2H), 1.72 (m, 2H), 1.60 (m, 1H), 0.96 (d, 3H), 0.91 (d, 3H). MS (M+1): 528.2.

후처리

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by HPLC (column: Boston Analytics Symmetrix ODS-H 150×30 mm, 5 μm; modifier: formic acid 0.225%; gradient: 10 to 80% MeCN in water)

출처 및 근거

ORD 기록
ord-fe66cf4a6cad41c5a36c58b430b578f4
출처 데이터셋
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08809342B2

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