Dichloromethane → 4-[bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1H-benzoimidazol-2-yl)-amide

HRID 1592606노트

반응식

HRID 1592606 반응식
[C:1](N1C=CN=C1)([N:3]1C=CN=C1)=[O:2].[NH2:13][C:14]1[NH:15][C:16]2[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=2[N:18]=1.CCN(C(C)C)C(C)C.[CH3:32][C:33]1[C:34]([CH2:39][N:40]([CH2:47][C:48]2[C:53]([CH3:54])=[CH:52][CH:51]=[CH:50][N:49]=2)[CH:41]2[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)=[N:35][CH:36]=[CH:37][CH:38]=1.[CH2:55]([Cl:57])[Cl:56]>>[CH2:55]([Cl:57])[Cl:56].[CH3:1][OH:2].[NH4+:3].[OH-:2].[NH:15]1[C:16]2[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=2[N:18]=[C:14]1[NH:13][C:1]([N:44]1[CH2:45][CH2:46][CH:41]([N:40]([CH2:47][C:48]2[C:53]([CH3:54])=[CH:52][CH:51]=[CH:50][N:49]=2)[CH2:39][C:34]2[C:33]([CH3:32])=[CH:38][CH:37]=[CH:36][N:35]=2)[CH2:42][CH2:43]1)=[O:2]

참가 물질

7

반응물 5

HCID 6344DichloromethaneHCID 136242-AminobenzimidazoleHCID 682631,1'-CarbonyldiimidazoleHCID 81531Diisopropylethylamine2회HCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

생성물 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 589969434-[bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid (1H-benzoimidazol-2-yl)-amide수율 43%

반응 조건

온도
60 °C

실험 절차

A solution of 1,1′-carbonyldiimidazole (0.0713 g, 0.44 mmol), 2-aminobenzimidazole (0.0533 g, 0.40 mmol), and DIPEA (0.14 mL, 0.80 mmol) in CH2Cl2 (4 mL) was stirred at room temperature for 2.5 hours. The mixture was concentrated, then dissolved in DMF (4 mL), and DIPEA (0.14 mL, 0.80 mmol) and COMPOUND 249 (0.1242 g, 0.40 mmol) were added. The mixture stirred at 60° C. for 20 hours, then concentrated. Saturated NaHCO3 (15 mL) was added and extracted with CH2Cl2 (3×40 mL). The combined organic extracts were washed with brine (2×30 mL), dried (Na2SO4), filtered and concentrated. Purification of the crude material by column chromatography on silica gel (75:1:1 then 50:1:1 CH2Cl2-MeOH—NH4OH) provided 0.0919 g (43%) of COMPOUND 347 as a white solid. 1H NMR (CDCl3) δ 1.66-1.70 (m, 4H), 1.94 (d, 2H, J=12.6 Hz), 2.07 (s, 6H), 2.69-2.77 (m, 3H), 3.81 (s, 4H), 4.41 (d, 2H, J=13.5 Hz), 7.06-7.15 (m, 4H), 7.29-7.31 (m, 2H), 7.36 (d, 2H, J=7.5 Hz), 8.33 (d, 2H, J=3.0 Hz). 13C NMR (CDCl3) 18.36, 27.60, 44.78, 54.93, 57.89, 112.76, 122.11, 122.77, 133.77, 138.41, 146.22, 152.31, 157.51, 158.32. ES-MS m/z 470.3 (M+H). Anal. Calcd. for C27H31N7.0.7CH2Cl2O.0.1CH4O: C, 62.74; H, 6.21; N, 18.42. Found: C, 63.02; H, 6.24; N, 18.22.

후처리

  1. concentrationThe mixture was concentrated
  2. dissolutiondissolved in DMF (4 mL)
  3. concentrationconcentrated
  4. additionSaturated NaHCO3 (15 mL) was added
  5. extractionextracted with CH2Cl2 (3×40 mL)
  6. washThe combined organic extracts were washed with brine (2×30 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the crude material by column chromatography on silica gel (75:1:1

출처 및 근거

ORD 기록
ord-c1e0e6b9a15e48fea6ac280711cc0231
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07291631B2

반응 노트

불러오는 중…