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Potassium Carbonate → 1-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(4-(piperidin-3-yl)-1H-1,2,3-triazol-1-yl)-1H-benzo[d]imidazole

HRID 2178307
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HRID 2178307 반응식
I[C:2]1[CH:29]=[CH:28][C:5]2[N:6]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]4[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=4)=[C:12]([O:26][CH3:27])[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.Cl.[C:31]([CH:33]1[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]1)#[CH:32].[N-:39]=[N+:40]=[N-:41].[Na+].[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O.CN(C)[C@@H]1CCCC[C@H]1N.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O.[OH-].[NH4+].[Cu]I>[CH3:27][O:26][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][C:13]=1[O:16][CH2:17][C:18]1[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=1)[CH2:9][N:6]1[C:5]2[CH:28]=[CH:29][C:2]([N:39]3[CH:32]=[C:31]([CH:33]4[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]4)[N:41]=[N:40]3)=[CH:3][C:4]=2[N:8]=[CH:7]1
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참가 물질

11

반응물 6

HCID 11430Potassium CarbonateHCID 33557Sodium AzideHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 534011233-Ethynylpiperidine hydrochlorideHCID 66586226sodium L-ascorbic acidHCID 1181141105-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazole

생성물 1

HCID 1180097781-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(4-(piperidin-3-yl)-1H-1,2,3-triazol-1-yl)-1H-benzo[d]imidazole수율 160.1%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 14923Ammonium Hydroxide용매

실험 절차

To a suspension of 5-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazole (0.32 g, 0.63 mmol) in dimethyl sulfoxide (4 mL) and water (1 mL) was added 3-ethynylpiperidine hydrochloride (0.11 g, 0.75 mmol), sodium azide (0.051 g, 0.79 mmol), L-ascorbic acid sodium salt (0.025 g, 0.13 mmol), trans-N,N-dimethylcyclohexane-1,2-diamine (0.023 mg, 0.158 mmol), potassium carbonate (0.13 g, 0.95 mmol), and copper(I) iodide (0.024 g, 0.13 mmol). The resulting blue mixture was allowed to stir at room temperature. After 16 h, the yellow mixture was diluted with 5N ammonium hydroxide solution and extracted with chloroform (2×30 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to provide 0.53 g of a yellow oil. Chromatographic purification (Combi-Flash, 24 g SiO2 gold column, 1-10% 2M ammonia in methanol/dichloromethane elute) afforded 0.15 g (45%) of the product as a white foamy solid: 1H NMR (400 MHz, DMSO-d6) δ 8.61-8.53 (m, 2H), 8.20 (d, J=2.4 Hz, 1H), 8.11 (d, J=1.9 Hz, 1H), 7.79-7.71 (m, 3H), 7.12 (d, J=1.9 Hz, 1H), 7.03 (d, J=8.2 Hz, 1H), 6.89-6.80 (m, 2H), 5.46 (s, 2H), 4.97 (s, 2H), 3.84 (s, 3H), 3.73 (s, 3H), 3.25-3.16 (m, 1H), 3.01-2.91 (m, 1H), 2.90-2.80 (m, 1H), 2.68-2.51 (m, 2H), 2.12-2.03 (m, 1H), 1.72-1.44 (m, 3H) ppm; (M+1)=526.

후처리

  1. extractionextracted with chloroform (2×30 mL)
  2. dry with materialThe combined organic phases were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-a2ed622c8e734a2ea933ecdfb726a7d5
출처 데이터셋
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09067914B1

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