Dimethylformamide → 10-Bromo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide

HRID 575046Notes

Reaction equation

HRID 575046 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[CH:12]1[CH2:16][CH:10]([CH2:11]1)[N:9]1[C:5]2=[N:6][C:7](I)=[CH:8]1.C[Si](N[Si](C)(C)C)(C)C.C[N:28](C)[CH:29]=[O:30]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[CH:12]1[CH2:16][CH:10]([CH2:11]1)[N:9]1[C:5]2=[N:6][C:7]([C:29]([NH2:28])=[O:30])=[CH:8]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 13838HexamethyldisilazaneHCID 8669307410-Bromo-2-iodo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine

Product 1

HCID 8669308110-Bromo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamideYield 83%

Conditions

Temperature
60 °C

Procedure

Into a 2-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed 9-bromo-4-iodo-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene (65 g, 162.08 mmol, 1.00 equiv), N,N-dimethylformamide (1.2 L), HMDS (208 g, 1.29 mol, 8.00 equiv), and Pd(PPh3)2C1 (9.1 g, 0.08 equiv). To the above CO (2 atm) was introduced in. The resulting solution was stirred at 60° C. for 2 h. This reaction was repeated for 3 more times. The reaction mixture was cooled to 40° C. and quenched by the addition of 1500 mL of water. The solids were collected by filtration and washed with 3×500 mL of water. The solids were diluted with 2 L of EA and stirred at room temperature for 1 h. The solids were collected by filtration. The filter cake was diluted with 2 L of EA and stirred at 50° C. for 1 h. The solids were collected by filtration and dried to afford 172 g (83%) of 9-bromo-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-4-carboxamide as a brown solid. LC-MS: 318 [M+1]+1H-NMR (DMSO, 300 MHz, ppm): □ 18.75 (s, 1H), 7.85 (s, 1H), 7.58 (s, 1H), 7.44-4.44 (dd, 1H), 7.23-7.25 (dd, 1H), 7.14 (s, 1H), 4.89-4.95 (m, 1H), 3.67-3.73 (m, 1H), 3.04-3.12 (m, 2H), 1.64-1.68 (m, 2H).

Workup

  1. customInto a 2-L 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureThe reaction mixture was cooled to 40° C.
  4. customquenched by the addition of 1500 mL of water
  5. filtrationThe solids were collected by filtration
  6. washwashed with 3×500 mL of water
  7. additionThe solids were diluted with 2 L of EA
  8. stirringstirred at room temperature for 1 h
  9. filtrationThe solids were collected by filtration
  10. additionThe filter cake was diluted with 2 L of EA
  11. stirringstirred at 50° C. for 1 h
  12. filtrationThe solids were collected by filtration
  13. customdried

Sources & evidence

ORD record
ord-b8ebf0a43b9f4c1399553e1e932860ac
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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