1,1'-Carbonyldiimidazole → 4-[bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amide

HRID 251188

반응식

HRID 251188 반응식
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].S(O)(O)(=O)=O.[NH2:18][C:19]1[NH:20][CH:21]=[CH:22][N:23]=1.CCN(C(C)C)C(C)C.[CH3:33][C:34]1[C:35]([CH2:40][N:41]([CH2:48][C:49]2[C:54]([CH3:55])=[CH:53][CH:52]=[CH:51][N:50]=2)[CH:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)=[N:36][CH:37]=[CH:38][CH:39]=1>C(Cl)Cl.CN(C=O)C>[NH:20]1[CH:21]=[CH:22][N:23]=[C:19]1[NH:18][C:1]([N:45]1[CH2:46][CH2:47][CH:42]([N:41]([CH2:48][C:49]2[C:54]([CH3:55])=[CH:53][CH:52]=[CH:51][N:50]=2)[CH2:40][C:35]2[C:34]([CH3:33])=[CH:39][CH:38]=[CH:37][N:36]=2)[CH2:43][CH2:44]1)=[O:2]

참가 물질

7

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531Diisopropylethylamine2회HCID 135136Bis(2-amino-1H-imidazole) sulphateHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

생성물 1

HCID 589971064-[bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1H-imidazol-2-yl)-amide수율 17%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

반응 조건

온도
60 °C

실험 절차

A solution of 1,1′-carbonyldiimidazole (0.0924 g, 0.57 mmol), 2-aminoimidazole sulfate (0.0687 g, 0.52 mmol), and DIPEA (0.36 mL, 2.08 mmol) in CH2Cl2 (6 mL) and DMF (6 mL) was stirred at room temperature for 4.5 hours. The mixture was concentrated to rid of CH2Cl2, and DIPEA (0.36 mL, 2.08 mmol) and COMPOUND 249 (0.1614 g, 0.52 mmol) were added. The mixture stirred at 60° C. for 19 hours, then concentrated. Saturated NaHCO3 (15 mL) was added and extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Purification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH) provided 37.1 mg (16%) COMPOUND 345 as a white solid. 1H NMR (CDCl3) δ 1.66-1.70 (m, 2H), 1.93-1.97 (m, 2H), 2.08 (s, 6H), 2.72 (t, 3H, J=10.8 Hz), 3.82 (s, 4H), 4.32 (d, 2H, J=11.4 Hz), 6.70 (s, 2H), 7.07-7.09 (m, 2H), 7.36 (d, 2H, J=7.2 Hz), 8.34 (s, 2H). 13C NMR (CDCl3) 18.37, 27.61, 44.75, 54.96, 57.81, 122.81, 133.79, 138.43, 145.43, 146.30, 155.71, 157.54. ES-MS m/z 420.1 (M+H). Anal. Calcd. for C23H29N7O.0.3CH2Cl2: C, 62.89; H, 6.70; N, 22.03. Found: C, 62.84; H, 6.93; N, 21.82.

후처리

  1. concentrationThe mixture was concentrated
  2. additionwere added
  3. concentrationconcentrated
  4. additionSaturated NaHCO3 (15 mL) was added
  5. extractionextracted with CH2Cl2 (3×30 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH)

출처 및 근거

ORD 기록
ord-a824a137c40b4ec7a5f214a3e3529515
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863293B2

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