Dimethylformamide → HCID 58203815, compound

HRID 1849080Notes

Reaction equation

HRID 1849080 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[CH:29]=[CH:28][C:9]3[C:10]4[N:11]=[C:12]([C:18]5[N:19]([CH2:23][C:24]([F:27])([F:26])[F:25])[N:20]=[CH:21][N:22]=5)[S:13][C:14]=4[CH2:15][CH2:16][O:17][C:8]=3[CH:7]=2)[CH:3]=[N:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.Br[CH2:42][CH2:43][OH:44]>O.C(OCC)(=O)C>[F:27][C:24]([F:26])([F:25])[CH2:23][N:19]1[C:18]([C:12]2[S:13][C:14]3[CH2:15][CH2:16][O:17][C:8]4[CH:7]=[C:6]([C:4]5[CH:3]=[N:2][N:1]([CH2:42][CH2:43][OH:44])[CH:5]=5)[CH:29]=[CH:28][C:9]=4[C:10]=3[N:11]=2)=[N:22][CH:21]=[N:20]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 108982-BromoethanolHCID 53235142HCID 53235142, compound

Product 1

HCID 58203815HCID 58203815, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 8-(1H-Pyrazol-4-yl)-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (0.30 g, 0.00072 mol) and Cesium Carbonate (0.28 g, 0.00086 mol) in N,N-Dimethylformamide (1.5 mL, 0.019 mol) was stirred at room temperature for 5 minutes. 2-Bromoethanol (0.061 mL, 0.00086 mol) was added and the reaction was stirred at 70° C. overnight. The mixture was cooled to room temperature and ethyl acetate and water were added to the reaction. The aqueous layer was extracted 3 times with ethyl acetate and the combined organics were washed with water, dried with MgSO4, and concentrated. The crude was purified by reverse-phase HPLC to give (48.4 mg) as a colorless solid. MS(ESI+) 463.1. 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H), 8.27 (d, J=8.3, 1H), 8.24 (s, 1H), 7.97 (s, 1H), 7.44 (dd, J=8.3, 1.6, 1H), 7.31 (d, J=1.5, 1H), 5.86 (q, J=8.7, 2H), 4.91 (t, J=5.3, 1H), 4.40 (t, J=4.9, 2H), 4.16 (t, J=5.6, 2H), 3.77 (q, J=5.6, 2H), 3.47 (t, J=4.9, 2H)

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe aqueous layer was extracted 3 times with ethyl acetate
  3. washthe combined organics were washed with water
  4. dry with materialdried with MgSO4
  5. concentrationconcentrated
  6. customThe crude was purified by reverse-phase HPLC
  7. customto give (48.4 mg) as a colorless solid

Sources & evidence

ORD record
ord-67c6f787e88b485fac5ce8fc921b82a0
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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