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

HRID 251151

반응식

HRID 251151 반응식
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C:14]1[N:18]([CH3:19])[C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[N:15]=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>CN(C=O)C>[CH3:19][N:18]1[C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[N:15]=[C:14]1[NH:13][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

6

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 741872-Amino-1-methylbenzimidazoleHCID 81531Diisopropylethylamine2회HCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

생성물 1

HCID 589970074-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1-methyl-1H-benzoimidazol-2-yl)-amide수율 27%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 1,1′-carbonyldiimidazole (80.1 mg, 0.494 mmol), 2-amino-1-methylbenzimidazole (70.8 mg, 0.481 mmol), and DIPEA (0.17 mL, 0.97 mmol) in DMF (5 mL) was stirred at room temperature for 2.5 h. To this solution was added DIPEA (0.17 mL, 0.97 mmol) and COMPOUND 249 (149 mg, 0.479 mmol), and the resultant solution was stirred at 60° C. overnight. The solution was concentrated to dryness, treated with saturated aqueous NaHCO3 (30 mL), and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 92:4:4) provided COMPOUND 290 (62 mg, 27%) as a white solid. 1H NMR (CDCl3) δ 1.63-1.76 (m, 2H), 1.80-2.05 (m, 2H), 2.10 (s, 6H), 2.43-2.80 (m, 3H), 3.54 (s, 3H), 3.83 (s, 4H), 4.61 (br s, 1H), 4.90 (br s, 1H), 7.04-7.20 (m, 6H), 7.36 (d, 2H, J=7.2 Hz), 8.35 (d, 2H, J=1.2 Hz); 13C NMR (CDCl3) 18.43, 27.22, 28.22, 42.96, 45.27, 55.07, 58.34, 108.42, 110.29, 122.33, 122.36, 122.72, 129.12, 131.10, 133.84, 138.37, 146.25, 154.51, 157.80, 163.72; ES-MS m/z 506 (M+Na). Anal. Calcd. for C28H33N7O.0.9H2O: C, 67.28; H, 7.02; N, 19.62. Found: C, 67.19; H, 6.97; N, 19.50.

후처리

  1. concentrationThe solution was concentrated to dryness
  2. additiontreated with saturated aqueous NaHCO3 (30 mL)
  3. extractionextracted with CH2Cl2 (3×15 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude material by flash chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 92:4:4)

출처 및 근거

ORD 기록
ord-fbb3d68d94aa42a89a4f6ad2d4c30ee9
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863293B2

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