Dimethylformamide → HCID 58203704, compound

HRID 2385685Notes

Reaction equation

HRID 2385685 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[S:18][C:17]3[C:16]4[CH:19]=[CH:20][C:21]([C:23]5[CH:24]=[N:25][NH:26][CH:27]=5)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.Br[CH2:40][CH2:41][OH:42]>O.C(OCC)(=O)C>[CH:1]([N:4]1[C:8]([C:9]2[S:18][C:17]3[C:16]4[CH:19]=[CH:20][C:21]([C:23]5[CH:27]=[N:26][N:25]([CH2:40][CH2:41][OH:42])[CH:24]=5)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 108982-BromoethanolHCID 57900381HCID 57900381, compound

Product 1

HCID 58203704HCID 58203704, compoundYield 39.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 1-Isopropyl-5-[8-(1H-pyrazol-4-yl)-4,5-dihydro-6-oxa-1-thia-benzo[e]azulen-2-yl]-1H-[1,2,4]triazole (0.23 g, 0.61 mmol) and cesium carbonate (0.40 g, 0.0012 mol) in N,N-dimethylformamide (1.8 mL, 0.023 mol) was stirred at room temperature for 5 minutes. 2-Bromoethanol (0.086 mL, 0.0012 mol) was added and the reaction was heated to 110° C. overnight. The mixture was cooled to room temperature. Ethyl acetate and water were added and the aqueous layer was extracted 3× with ethyl acetate. The organic phases were combined, dried with MgSO4, and concentrated. The crude was purified by reverse-phase HPLC to give 101.8 mg of 145 as a colorless solid. MS (ESI+) 422.1. 1H NMR (400 MHz, DMSO) δ 8.21 (s, 1H), 8.00 (s, 1H), 7.93 (s, 1H), 7.66 (d, J=8.2, 1H), 7.52 (s, 1H), 7.32 (dd, J=8.2, 1.6, 1H), 7.27 (d, J=1.5, 1H), 5.10-4.95 (m, 1H), 4.90 (t, J=5.3, 1H), 4.34 (t, J=5.0, 2H), 4.15 (t, J=5.6, 2H), 3.77 (q, J=5.5, 2H), 3.29-3.24 (m, 2H), 1.48 (d, J=6.5, 6H)

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionthe aqueous layer was extracted 3× with ethyl acetate
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated
  5. customThe crude was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-c957d9270fad4c7d91940332d8956632
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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