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 1599068Notes

Reaction equation

HRID 1599068 reaction equation
[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]

Participants

6

Reactant 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

Product 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}-amideYield 11.9%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-d8ba41b7ccc740acab4fffe5d3714b4a
Source dataset
uspto-grants-1998_04
Patent number
US05739129

Reaction notes

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