Sodium Hydroxide → 2-(4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-1-yl)-N,2-dimethylpropanamide

HRID 1800078Notes

Reaction equation

HRID 1800078 reaction equation
[OH-].[Na+].Br[C:4]([CH3:10])([CH3:9])[C:5]([NH:7][CH3:8])=[O:6].FC(F)(F)C(O)=O.[CH:18]([N:21]1[C:25]([C:26]2[N:35]=[C:34]3[N:28]([CH2:29][CH2:30][O:31][C:32]4[CH:39]=[C:38]([CH:40]5[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]5)[CH:37]=[CH:36][C:33]=43)[CH:27]=2)=[N:24][CH:23]=[N:22]1)([CH3:20])[CH3:19]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH:18]([N:21]1[C:25]([C:26]2[N:35]=[C:34]3[C:33]4[CH:36]=[CH:37][C:38]([CH:40]5[CH2:45][CH2:44][N:43]([C:4]([CH3:10])([CH3:9])[C:5]([NH:7][CH3:8])=[O:6])[CH2:42][CH2:41]5)=[CH:39][C:32]=4[O:31][CH2:30][CH2:29][N:28]3[CH:27]=2)=[N:24][CH:23]=[N:22]1)([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 2875602-Bromo-N,2-dimethylpropanamideHCID 670507222-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt

Product 1

HCID 710146972-(4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-1-yl)-N,2-dimethylpropanamideYield 41.2%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalyst2×HCID 6344DichloromethaneSolvent3×

Procedure

A biphasic mixture of 50% aqueous sodium hydroxide (2 mL) and DCM (2.5 mL) was treated with 2-bromo-2,N-dimethyl-propionamide (121 mg, 0.67 mmol), tetrabutylammonium bromide (118 mg, 0.37 mmol) and a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt (300 mg, 0.61 mmol) in DCM (1 mL). The resultant mixture was stirred at RT for 3 h before the addition of further tetrabutylammonium bromide (118 mg, 0.37 mmol) and stirring at RT for 18 h. The reaction mixture was diluted with DCM and washed with water. The combined aqueous extracts were washed with DCM and the combined organic extracts dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 5% MeOH in DCM) followed by trituration in diethyl ether to give 248 as a cream solid (120 mg, 41%). 1H NMR δ (ppm) (DMSO-d6): 8.27 (1H, d, J=8.26 Hz), 7.86 (1H, d, J=0.63 Hz), 7.85 (1H, s), 7.64 (1H, m), 7.02 (1H, dd, J=8.34, 1.75 Hz), 6.91 (1H, d, J=1.70 Hz), 5.88-5.78 (1H, m), 4.48-4.42 (4H, m), 2.74 (2H, d, J=10.86 Hz), 2.59 (3H, d, J=4.75 Hz), 2.17-2.08 (2H, m), 1.75-1.69 (4H, m), 1.43 (6H, d, J=6.60 Hz), 1.05 (6H, s). 1 Proton obscured by solvent peak. LCMS: RT=2.78 min, M+H+=478

Workup

  1. washwashed with water
  2. washThe combined aqueous extracts were washed with DCM
  3. dry with materialthe combined organic extracts dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9c97129117cf4a8f80a55be6f336591a
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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