Potassium Carbonate → 2-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-acetamide

HRID 708064Notes

Reaction equation

HRID 708064 reaction equation
OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([C:12]2[CH:33]=[CH:32][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH:29]([CH3:31])[CH3:30])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH2:9]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:41][C:42]([NH2:44])=[O:43]>C1COCC1>[CH:29]([N:25]1[C:24]([C:18]2[S:19][C:20]3[CH2:21][CH2:22][O:23][C:14]4[CH:13]=[C:12]([CH:10]5[CH2:11][N:8]([CH2:41][C:42]([NH2:44])=[O:43])[CH2:9]5)[CH:33]=[CH:32][C:15]=4[C:16]=3[N:17]=2)=[N:28][CH:27]=[N:26]1)([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 696322-BromoacetamideHCID 866523168-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

Product 1

HCID 582042442-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 8-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 235 (200 mg, 0.42 mmol) in THF (3 mL) was added potassium carbonate (174 mg, 1.26 mmol) and 2-bromoacetamide (63 mg, 0.46 mmol) and the reaction mixture was stirred at RT for 18 hours. The volatiles were evaporated in vacuo and the residue partitioned between DCM and an aqueous saturated sodium bicarbonate solution. The organic layer was washed with water followed by brine, dried (MgSO4), concentrated in vacuo and the residue purified by flash chromatography (SiO2, 0-5% MeOH in DCM) to give 319 isolated as a cream solid after freeze drying from methanol and water (40 mg, 22%). LCMS: RT=3.03 min, [M+H]+=425. 1H NMR δ (ppm) (DMSO-d6): 8.26 (1H, d, J=8.18 Hz), 8.05 (1H, s), 7.20 (1H, dd, J=8.24, 1.83 Hz), 7.08 (1H, s), 7.00 (2H, d, J=1.87 Hz), 5.83-5.73 (1H, m), 4.34-4.28 (2H, m), 3.69-3.62 (2H, m), 3.63-3.52 (1H, m), 3.41-3.35 (2H, m), 3.21-3.14 (2H, m), 2.99 (2H, s), 1.50 (6H, d, J=6.59 Hz)

Workup

  1. customThe volatiles were evaporated in vacuo
  2. customthe residue partitioned between DCM
  3. washThe organic layer was washed with water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customthe residue purified by flash chromatography (SiO2, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-cce3d500d876443c878846b0019af733
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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