3-Bromopyridine → 2-(3-Allyl-3-methyl-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-[4-methoxyphenyl]acetamide

HRID 343186Notes

Reaction equation

HRID 343186 reaction equation
[CH2:1]([C:4]1([CH3:32])[C:10](=[O:11])[N:9]([CH2:12][C:13]([N:15]([CH:24]([CH3:26])[CH3:25])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[O:14])[C:8]2[CH:27]=[CH:28][CH:29]=[CH:30][C:7]=2[NH:6][C:5]1=[O:31])[CH:2]=[CH2:3].Br[C:34]1[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=1.C([O-])(=O)C.[K+]>CN(C=O)C.CCOC(C)=O.[Cu]>[CH2:1]([C:4]1([CH3:32])[C:10](=[O:11])[N:9]([CH2:12][C:13]([N:15]([CH:24]([CH3:26])[CH3:25])[C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)=[O:14])[C:8]2[CH:27]=[CH:28][CH:29]=[CH:30][C:7]=2[N:6]([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[C:5]1=[O:31])[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 122863-BromopyridineHCID 517044Potassium AcetateHCID 676971062-(3-Allyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxyphenyl) acetamide

Product 1

HCID 676972302-(3-Allyl-3-methyl-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-[4-methoxyphenyl]acetamideYield 53%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
125 °C

Procedure

To a stirring solution of 2.5 g (5.74 mmol) of 2-(3-Allyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxyphenyl) acetamide, prepared as in Part A, in 25 mL of DMF is added 1.81 g (11.5 mmol, 2 equiv.) of 3-bromopyridine, 1.12 g (11.5 mmol, 2 equiv.) of potassium acetate, and 364 mg (11.5 mmol) of copper powder. The suspension is heated to 125° C. for 4 h and then cooled to RT. It is diluted with 350 mL EtOAc and filtered through a bed of celite. The filtrate is washed with H2O (2×300 mL), conc. NH4OH (2×150 mL) and then dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel flash column chromatography using hexane/EtOAc 1/1 as eluent afforded 1.56 g of 2-(3-Allyl-3-methyl-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-[4-methoxyphenyl]acetamide as an oil: 1H NMR (CDCl3, 300 MHz) δ8.51 (m, 2H), 7.68 (d, 1H, J=9), 7.39-6.93 (m, 8H), 6.71 (d, 1H, J=8), 5.78-5.64 (m, 1H), 5.08-5.00 (m, 2H), 4.72 (d, 1H, J=16), 4.39 (d, 1H, J=17), 4.08 (m, 1H), 3.85 (s, 3H), 3.81-3.79 (m, 1H), 2.11 (d, 1H, J=8), 1.77 (s, 1H), 1.60 (s, 2H), 1.21-1.07 (m, 6H).

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered through a bed of celite
  3. washThe filtrate is washed with H2O (2×300 mL), conc. NH4OH (2×150 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvents removed in vacuo
  6. customPurification by silica gel flash column chromatography

Sources & evidence

ORD record
ord-2a8de557281749a2941b888f86f5e7e7
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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