Potassium Carbonate → 2-(4-(2-(1-isopropyl-3-(methoxymethyl)-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 886324Notes

Reaction equation

HRID 886324 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][C:13]([CH2:36][O:37][CH3:38])=[N:12]1)([CH3:10])[CH3:9].Br[CH2:40][C:41]([NH2:43])=[O:42].C(=O)([O-])[O-].[K+].[K+]>C1COCC1.C(Cl)Cl.O>[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[C:23]4[CH:26]=[CH:27][C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:40][C:41]([NH2:43])=[O:42])[CH2:32][CH2:31]5)=[CH:29][C:22]=4[O:21][CH2:20][CH2:19][N:18]3[CH:17]=2)=[N:14][C:13]([CH2:36][O:37][CH3:38])=[N:12]1)([CH3:10])[CH3:9]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 696322-BromoacetamideHCID 670506872-(2-Isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetate salt

Product 1

HCID 582050202-(4-(2-(1-isopropyl-3-(methoxymethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-1-yl)acetamideYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 2-(2-isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetate salt (99 mg, 0.18 mmol) in THF (1.8 mL) was treated with 2-bromoacetamide (109 mg, 0.2 mmol) followed by potassium carbonate (56 mg, 0.41 mmol) and the reaction mixture stirred at RT before being diluted with DCM and water. The aqueous layer was extracted twice with DCM and the combined organic extracts washed with saturated aqueous sodium bicarbonate followed by brine then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was dissolved in methanol, the solution cooled to 0° C., and treated with water to form a precipitate which was filtered off and washed with cold methanol/water to give a white solid. The solid was azeotroped with methanol then diethyl ether to give 308 as a white solid (38 mg, 43%). LCMS: RT=2.66 min, [M+H]+=480. 1H NMR 400 MHz (DMSO-d6) δ: 8.39 (1H, d, J=8.32 Hz), 8.16 (1H, s), 7.09-7.08 (1H, m), 6.97 (1H, s), 5.76-5.74 (1H, m), 4.58 (4H, d, J=14.42 Hz), 4.51 (2H, s), 3.96 (2H, s), 3.60 (2H, d, J=11.71 Hz), 3.37 (3H, s), 3.20 (2H, m), 2.86 (1H, m), 2.03 (4H, m), 1.53 (6H, d, J=6.57 Hz)

Workup

  1. extractionThe aqueous layer was extracted twice with DCM
  2. washthe combined organic extracts washed with saturated aqueous sodium bicarbonate
  3. dry with materialthen dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resultant residue was dissolved in methanol
  7. temperaturethe solution cooled to 0° C.
  8. additiontreated with water
  9. customto form a precipitate which
  10. filtrationwas filtered off
  11. washwashed with cold methanol/water
  12. customto give a white solid
  13. customThe solid was azeotroped with methanol

Sources & evidence

ORD record
ord-836bc232c7c34195b336b6e123583b32
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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