N-Iodosuccinimide → 10-bromo-9-fluoro-3-iodo-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[F:16])[CH:12]1[CH2:17][CH:10]([CH2:11]1)[N:9]1[C:5]2=[N:6][C:7]([C:18]([NH2:20])=[O:19])=[CH:8]1.[I:21]N1C(=O)CCC1=O>CN(C=O)C>[F:16][C:15]1[C:2]([Br:1])=[CH:3][C:4]2[C:5]3[N:9]([CH:10]4[CH2:11][CH:12]([C:13]=2[CH:14]=1)[CH2:17]4)[C:8]([I:21])=[C:7]([C:18]([NH2:20])=[O:19])[N:6]=3Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 70 °C
Procedure
9-bromo-10-fluoro-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-4-carboxamide (20.00 g, 59.5 mmol) and N-iodosuccinimide (2.00 equiv., 27.60 g, 119 mmol) were dissolved in DMF (300 mL, 5 mL/mmol) and stirred at 70° C. overnight. After 24 hours, the solution was concentrated in vacuo and diluted with water, then triturated for 1 hour and filtered. The solid was redissolved in ethyl acetate, triturated for 1 hour, and filtered to afford 23.93 g (87% yield) of the titled compound as a light orange solid, 1H NMR (400 MHz, DMSO) δ 8.92 (d, J=7.4 Hz, 1H), 7.74 (br s, 1H), 7.37 (d, J=9.5 Hz, 1H), 7.16 (br s, 1H), 5.12 (td, J=6.7, 4.1 Hz, 1H), 3.68 (td, J=7.6, 4.1 Hz, 1H), 3.25-3.11 (m, 2H), 1.78-1.64 (m, 2H).
Workup
- waitAfter 24 hours
- concentrationthe solution was concentrated in vacuo
- additiondiluted with water
- customtriturated for 1 hour
- filtrationfiltered
- dissolutionThe solid was redissolved in ethyl acetate
- customtriturated for 1 hour
- filtrationfiltered
Sources & evidence
- ORD record
- ord-3e259d9c61ad463cad8341141c0eb642
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034866B2
Reaction notes
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