Potassium Cyanide → 10-Bromo-3-cyano-9-fluoro-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide

HRID 575141Notes

Reaction equation

HRID 575141 reaction equation
[C-:1]#[N:2].[K+].[Br:4][C:5]1[C:6]([F:23])=[CH:7][C:8]2[O:14][CH2:13][CH2:12][N:11]3[C:15](I)=[C:16]([C:18]([NH2:20])=[O:19])[N:17]=[C:10]3[C:9]=2[CH:22]=1>CN(C=O)C.[Cu]I>[Br:4][C:5]1[C:6]([F:23])=[CH:7][C:8]2[O:14][CH2:13][CH2:12][N:11]3[C:15]([C:1]#[N:2])=[C:16]([C:18]([NH2:20])=[O:19])[N:17]=[C:10]3[C:9]=2[CH:22]=1

Participants

5

Reactant 2

HCID 9032Potassium CyanideHCID 8669305210-Bromo-9-fluoro-3-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 8669316310-Bromo-3-cyano-9-fluoro-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

Potassium Cyanide (0.8 eq) and Copper (I) Iodide (0.2 eq) were added to solution of 10-bromo-9-fluoro-3-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (0.05 g) in DMF (3 ml/mmol). The reaction was heated overnight at 150° C., filtered and purified by reverse phase hplc to give 10-bromo-3-cyano-9-fluoro-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide. This intermediate was reacted with 2-Methyl-3-butyne-ol similar to as described in Procedure E to afford 12 mg of 3-cyano-9-fluoro-10-(3-hydroxy-3-methyl-but-1-ynyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide following reverse phase hplc purification. MS (Q1) 355 (M)+. 1H NMR (400 MHz, DMSO) δ 8.69-8.56 (m, 1H), 8.04 (s, 1H), 7.64 (s, 1H), 7.14-7.00 (m, 1H), 5.51 (d, J=10.2 Hz, 1H), 4.63-4.57 (m, 2H), 4.56-4.49 (m, 2H), 1.49 (s, 6H).

Workup

  1. filtrationfiltered
  2. custompurified by reverse phase

Sources & evidence

ORD record
ord-b6a046f11a1644e285a9955f1e54a4ea
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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