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2-Aminopyridine → 4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid pyridin-2-ylamide

HRID 251144
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HRID 251144 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8](N1C=CN=C1)(N1C=CN=C1)=[O:9].[CH3:20][C:21]1[C:22]([CH2:28][N:29]([CH2:36][C:37]2[C:42]([CH:43]([CH3:45])[CH3:44])=[CH:41][CH:40]=[CH:39][N:38]=2)[CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[N:23][CH:24]=[C:25]([CH3:27])[CH:26]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:8]([N:33]1[CH2:34][CH2:35][CH:30]([N:29]([CH2:28][C:22]2[C:21]([CH3:20])=[CH:26][C:25]([CH3:27])=[CH:24][N:23]=2)[CH2:36][C:37]2[C:42]([CH:43]([CH3:45])[CH3:44])=[CH:41][CH:40]=[CH:39][N:38]=2)[CH2:31][CH2:32]1)=[O:9]
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참가 물질

6

반응물 4

HCID 104392-AminopyridineHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 58997074(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

생성물 1

HCID 589971674-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid pyridin-2-ylamide수율 81%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 2-aminopyridine (69 mg, 0.73 mmol) in CH2Cl2 (5 mL) was added 1,1′-carbonyldiimidazole (122 mg, 0.75 mmol) and the reaction stirred at reflux for 2 h 15 min. after which a solution of (3,5-dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidine-4-yl-amine (87 mg, 0.247 mmol) in CH2Cl2 (3 mL) was added and the reaction stirred at reflux for 2.5 h. The solution was cooled, treated with saturated aqueous NaHCO3 (25 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 100:1:1 then 50:1:1) provided COMPOUND 284 (94 mg, 81%) as a colorless oil: 1H NMR (CDCl3) δ 0.92 (d, 6H, J=6.9 Hz), 1.62-1.75 (m, 2H), 1.92-1.98 (m, 3H), 2.16 (s, 3H), 2.28 (s, 3H), 2.72-2.85 (m, 4H), 3.77 (s, 2H), 3.83 (s, 2H), 4.17-4.21 (m, 2H), 6.92 (dd, 1H, J=6.6, 5.4 Hz), 7.14 (dd, 1H, J=7.8, 4.8 Hz), 7.24 (br s, 2H), 7.50 (dd, 1H, J=7.8, 1.2 Hz), 7.63 (dt, 1H, J=6.9, 1.8 Hz), 8.01 (d, 1H, J=8.4 Hz), 8.19 (s, 1H), 8.33 (dd, 1H, J=4.8, 1.5 Hz). 13C NMR (CDCl3) δ 18.29, 18.45, 23.60, 27.45, 44.80, 54.32, 57.34, 113.61, 118.62, 123.18, 132.28, 133.19, 133.86, 138.48, 139.06, 144.39, 146.08, 146.65, 147.81, 153.27, 154.03, 154.42, 156.23. ES-MS m/z 495 (M+Na). Anal. Calcd. for C28H36N6O.0.8CH2Cl2: C, 63.99; H, 7.01; N, 15.55. Found: C, 64.33; H, 7.28; N, 15.68.

후처리

  1. additionwas added
  2. stirringthe reaction stirred
  3. temperatureat reflux for 2.5 h
  4. temperatureThe solution was cooled
  5. extractionextracted with CH2Cl2 (3×20 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 100:1:1

출처 및 근거

ORD 기록
ord-cc7e47d5cb614867b18ef9cb4575a714
출처 데이터셋
uspto-grants-2011_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07863293B2

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