1-Hydroxybenzotriazole → rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-N-(tetrahydro-2H-pyran-4-ylmethyl)-4-(trifluoromethyl)pyrimidine-5-carboxamide

HRID 38777노트

반응식

HRID 38777 반응식
[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]([C:19](O)=[O:20])=[CH:11][N:10]=1.[O:22]1[CH2:27][CH2:26][CH:25]([CH2:28][NH2:29])[CH2:24][CH2:23]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>O.CN(C)C=O>[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[C:12]([C:19]([NH:29][CH2:28][CH:25]2[CH2:26][CH2:27][O:22][CH2:23][CH2:24]2)=[O:20])=[CH:11][N:10]=1

참가 물질

7

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27732104-AminomethyltetrahydropyranHCID 66720245rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid

생성물 1

HCID 66720248rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-N-(tetrahydro-2H-pyran-4-ylmethyl)-4-(trifluoromethyl)pyrimidine-5-carboxamide수율 87.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid (150 mg) and N,N-dimethyl formamide (3.0 mL) were added 1-(tetrahydro-2H-pyran-4-yl)methylamine (69 mg), 1-hydroxybenzotriazole (81 mg), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (115 mg) in this order at room temperature, and then the mixture was stirred at room temperature for 5 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and then the obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate). The obtained colorless oily substance was solidified using ethanol-water to obtain rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-N-(tetrahydro-2H-pyran-4-ylmethyl)-4-(trifluoromethyl)pyrimidine-5-carboxamide (173 mg) as a white solid.

후처리

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order, and then dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)

출처 및 근거

ORD 기록
ord-299d45b4838342a2804482f39acea01d
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524727B2

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