Potassium Carbonate → N-tert-butyl-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)acetamide

HRID 886276Notes

Reaction equation

HRID 886276 reaction equation
FC(F)(F)C(O)=O.[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=43)[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].C(=O)([O-])[O-].[K+].[K+].[C:42]([NH:46][C:47](=[O:50])[CH2:48]Cl)([CH3:45])([CH3:44])[CH3:43]>C1COCC1.C(Cl)Cl>[C:42]([NH:46][C:47](=[O:50])[CH2:48][N:33]1[CH2:34][CH2:35][CH:30]([C:28]2[CH:27]=[CH:26][C:23]3[C:24]4[N:18]([CH:17]=[C:16]([C:15]5[N:11]([CH:8]([CH3:10])[CH3:9])[N:12]=[CH:13][N:14]=5)[N:25]=4)[CH2:19][CH2:20][O:21][C:22]=3[CH:29]=2)[CH2:31][CH2:32]1)([CH3:45])([CH3:44])[CH3:43]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 222440N-tert-butyl-2-chloroacetamideHCID 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 51348057N-tert-butyl-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)acetamideYield 56%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension 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 THF (5 mL) was added potassium carbonate (295 mg, 2.13 mmol) and N-tert-butyl-2-chloro-acetamide (100 mg, 0.67 mmol). The mixture was stirred for 5 days before being diluted with DCM and washed with water (2×30 mL). The organic phase was dried (MgSO4) and concentrated in vacuo. The resultant residue was triturated in diethyl ether, affording 274 as a cream solid (169 mg, 0.34 mmol, 56%). LCMS: RT=3.12 min, [M+H]+=492. 1H NMR δ (ppm) (DMSO-d): 8.29 (1H, d, J=8.29 Hz), 7.86 (1H, d, J=0.63 Hz), 7.85 (1H, s), 7.15 (1H, s), 7.03 (1H, dd, J=8.36, 1.77 Hz), 6.89 (1H, d, J=1.71 Hz), 5.90-5.80 (1H, m), 4.48-4.41 (4H, m), 2.85 (2H, d, J=11.24 Hz), 2.81 (2H, s), 2.20-2.09 (2H, m), 1.78-1.67 (2H, m), 1.70-1.58 (2H, m), 1.44 (6H, d, J=6.60 Hz), 1.25 (9H, s). 1H obscured by solvent.

Workup

  1. washwashed with water (2×30 mL)
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue was triturated in diethyl ether

Sources & evidence

ORD record
ord-034b9dbd7d8a4f23b1734f12fa696b79
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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