Tris(hydroxymethyl)aminomethane → Ethyl 4-({[6-(3,5-difluorophenyl)pyridin-3-yl]carbonyl}amino)piperidine-1-carboxylate

HRID 602080노트

반응식

HRID 602080 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.[NH2:28][CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:31][CH2:30]1.N=C=N.C(O)C(N)(CO)CO>C(Cl)Cl>[F:8][C:6]1[CH:5]=[C:4]([C:9]2[N:10]=[CH:11][C:12]([C:13]([NH:28][CH:29]3[CH2:30][CH2:31][N:32]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:33][CH2:34]3)=[O:15])=[CH:16][CH:17]=2)[CH:3]=[C:2]([F:1])[CH:7]=1

참가 물질

7

반응물 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 757711-HydroxybenzotriazoleHCID 100867Ethyl 4-amino-1-piperidinecarboxylateHCID 160435CarbodiimideHCID 532230406-(3,5-Difluorophenyl)pyridine-3-carboxylic acid

생성물 1

HCID 59744016Ethyl 4-({[6-(3,5-difluorophenyl)pyridin-3-yl]carbonyl}amino)piperidine-1-carboxylate수율 16.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

6-(3,5-difluoro-phenyl)-nicotinic acid (55 mg, 0.23 mmol), HOBt (40 mg, 0.29 mmol), ethyl 4-aminopiperidine-1-carboxylate (23 mg, 0.13 mmol), and PS-carbodimide (350 mg) in DCM (5 ml) was shaken 12 h. After shaking, PS-trisamine (3 mg) was added and the reaction shaken for 4 h, then filtered and washed with 15% MeOH/DCM. The organic was concentrated and purified by reversed phase automatic chromatography to provide 8.3 mg (9%) of the title compound. 1H NMR (400 MHz, DMSO-d6) □ ppm 9.08 (1H, d, J=1.5 Hz), 8.51 (1H, d, J=7.3 Hz), 8.31 (1H, dd, J=8.2, 2.4 Hz), 8.19 (1 h, d, J=8.8 Hz), 7.89 (2H, br. s.), 4.03 (2H, br. s.), 4.05 (4H, d, J=7.3 Hz), 2.94 (2H, br. s.), 1.85 (2H, d, J=13.5 Hz), 1.48 (2H, br. s.), 1.20 (3H, t, J=7.1 Hz).

후처리

  1. stirringthe reaction shaken for 4 h
  2. filtrationfiltered
  3. washwashed with 15% MeOH/DCM
  4. concentrationThe organic was concentrated
  5. custompurified by reversed phase automatic chromatography

출처 및 근거

ORD 기록
ord-2f8f399826a847b29a86275083b16b00
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902373B2

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