Sodium Hydroxide → trans-racemic-2-(3-hydroxy-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 2044568Notes

Reaction equation

HRID 2044568 reaction equation
Cl.[CH:2]([N:5]1[C:9]([C:10]2[N:19]=[C:18]3[N:12]([CH2:13][CH2:14][O:15][C:16]4[CH:23]=[C:22]([C@@H:24]5[CH2:29][CH2:28][NH:27][CH2:26][C@H:25]5[OH:30])[CH:21]=[CH:20][C:17]=43)[CH:11]=2)=[N:8][CH:7]=[N:6]1)([CH3:4])[CH3:3].Br[C:32]([CH3:38])([CH3:37])[C:33]([NH:35][CH3:36])=[O:34].[OH-].[Na+]>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].C(Cl)Cl>[OH:30][C@H:25]1[C@H:24]([C:22]2[CH:21]=[CH:20][C:17]3[C:18]4[N:12]([CH:11]=[C:10]([C:9]5[N:5]([CH:2]([CH3:4])[CH3:3])[N:6]=[CH:7][N:8]=5)[N:19]=4)[CH2:13][CH2:14][O:15][C:16]=3[CH:23]=2)[CH2:29][CH2:28][N:27]([C:32]([CH3:38])([CH3:37])[C:33]([NH:35][CH3:36])=[O:34])[CH2:26]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 2875602-Bromo-N,2-dimethylpropanamideHCID 131729888trans-racemic-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-3-ol hydrochloride

Product 1

HCID 131729898trans-racemic-2-(3-hydroxy-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 37%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of trans-racemic-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-3-ol hydrochloride (199 mg, 0.46 mmol), 2-bromo-2-methyl-N-methyl propionamide (83 mg, 0.46 mmol), NaOH (2 mL, 50% aqueous solution), TBAB (16 mg, 0.05 mmol) and DCM (2.5 mL) was stirred vigorously at RT for 7.5 h. The phases were separated and the aqueous layer extracted three times with 10% methanol in DCM, the combined organic extracts washed with brine then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% methanol in DCM) to give 330 (84 mg, 37%). LCMS: RT=2.54 min, [M+H]+=494. 1H NMR 400 MHz (CDCl3) δ: 8.44 (1H, d, J=8.23 Hz), 7.87 (1H, s), 7.48 (1H, s), 7.17 (1H, br), 7.08 (1H, m), 6.86 (1H, s), 6.03-6.01 (1H, m), 4.77-4.07 (4H, m), 3.82 (1H, br), 3.17 (1H, m), 2.86 (3H, d, J=4.98 Hz), 2.85 (2H, m), 2.46 (1H, m), 2.27 (1H, m), 2.18 (1H, m), 1.90 (1H, m), 1.70 (1H, m), 1.61 (6H, m), 1.27 (6H, d, J=10.69 Hz)

Workup

  1. customThe phases were separated
  2. extractionthe aqueous layer extracted three times with 10% methanol in DCM
  3. washthe combined organic extracts washed with brine
  4. dry with materialthen dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bbec65583cc8435b941fc1da31c19598
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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