3-Bromopyridine → 1H-Indole-2-carboxylic acid {1[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide

HRID 1599068노트

반응식

HRID 1599068 반응식
[CH:1]([C:4]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)([C:30](=[O:32])[NH2:31])[N:5]1[C:11](=[O:12])[CH:10]([NH:13][C:14]([C:16]2[NH:17][C:18]3[C:23]([CH:24]=2)=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[C:9](=[O:25])[NH:8][C:7]2[CH:26]=[CH:27][CH:28]=[CH:29][C:6]1=2)([CH3:3])[CH3:2].Br[C:42]1[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=1.[K+].C([O-])(=O)C>CN(C=O)C.[Cu]>[CH:1]([C:4]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)([C:30](=[O:32])[NH2:31])[N:5]1[C:11](=[O:12])[CH:10]([NH:13][C:14]([C:16]2[NH:17][C:18]3[C:23]([CH:24]=2)=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[C:9](=[O:25])[N:8]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)[C:7]2[CH:26]=[CH:27][CH:28]=[CH:29][C:6]1=2)([CH3:3])[CH3:2]

참가 물질

6

반응물 3

HCID 122863-BromopyridineHCID 517044Potassium AcetateHCID 867524091H-Indole-2-carboxylic acid {1-[isopropyl-(4-methoxyphenyl)-carbamoylmethyl]-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide

생성물 1

HCID 867524081H-Indole-2-carboxylic acid {1[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide수율 11.9%

시약·촉매·용매 2

HCID 23978Copper촉매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

To a solution of 1H-Indole-2-carboxylic acid {1[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-2,3,4,5-tetrhydro-1H-benzo[b][1,4]diazepine-3-yl}amide (0.14 g, 0.26 mmol) and 3-bromopyridine (40 μL, 0.42 mmol)in DMF (1 mL) was added copper powder (46 mg, 0.73 mmol) and acetic acid potassium salt (38 mg, 0.73 mmol). The heterogenous solution was stirred at 100° C. for 15 h and subsequently hot filtered through celite and washed with methanol. The resulting precipitate was filtered and purified by RPHPLC (40-60% C. over 30 min) to yield the title compound (19 mg) as a white lyophile: Tr=8.7 min (40-60% C. over 30 min); 1HNMR (d6 -Acetone, 300 MHz) δ 10.98 (s, 1H), 9.02 (s, 1H), 8.76 (s, 1H), 7.85 (d, 1H, J=8.8), 7.5 (m, 15H), 5.68 (d, 1H, J=7.6), 5.02 (m, 1H), 4.65 (ABq, 2H, J=16.8, 135), 4.02 (s, 3H), 2.19 (d, 3H, J=2.0), 2.18 (d, 3H, J=2.0); low resolution MS(FAB) m/e 617 (MH+).

후처리

  1. filtrationsubsequently hot filtered through celite
  2. washwashed with methanol
  3. filtrationThe resulting precipitate was filtered
  4. custompurified by RPHPLC (40-60% C. over 30 min)

출처 및 근거

ORD 기록
ord-d8ba41b7ccc740acab4fffe5d3714b4a
출처 데이터셋
uspto-grants-1998_04
특허 번호
US05739129

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