Sodium Carbonate → HCID 53235215, compound

HRID 628083Notes

Reaction equation

HRID 628083 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]=[C:8]([N:14]4[C:18]([CH:19]([CH3:21])[CH3:20])=[N:17][CH:16]=[N:15]4)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][NH:35][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:19]([C:18]1[N:14]([C:8]2[S:9][C:10]3[CH2:11][CH2:12][O:13][C:4]4[CH:3]=[C:2]([C:32]5[CH:33]=[N:34][NH:35][CH:36]=5)[CH:23]=[CH:22][C:5]=4[C:6]=3[N:7]=2)[N:15]=[CH:16][N:17]=1)([CH3:21])[CH3:20]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57900120HCID 57900120, compound

Product 1

HCID 53235215HCID 53235215, compoundYield 20.1%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst2×HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A suspension of 8-bromo-2-(5-isopropyl-[1,2,4]triazol-1-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (84 mg, 0.21 mmol), 4,4,5,5-tetramethyl-2-(1H-pyrazol-4-yl)-1,3,2-dioxaborolane (62 mg, 0.32 mmol), tetrakis(triphenylphosphine) palladium (0) (24 mg, 0.021 mmol) and sodium carbonate (45 mg, 0.42 mmol) in acetonitrile (6 mL) and water (3 mL) under nitrogen was heated at 140° C. for 25 mins under microwave irradiation. More tetrakis(triphenylphosphine) palladium (0) (24 mg, 0.021 mmol) was added, and heating was pursued for 30 mins at 150° C. The reaction mixture was diluted with ethyl acetate and water. The organic layer was washed with brine, dried (Na2SO4), concentrated in vacuo and purified twice by flash chromatography (SiO2, gradient 50 to 75% ethyl acetate in cyclohexane, then 60% ethyl acetate in cyclohexane) to afford 484 as an off-white solid (16 mg, 20%). LCMS (Method C): RT=10.30 min, [M+H]+=379. 1H NMR (DMSO-d6): 12.98 (1H, bs), 8.28 (1H, bs), 8.18 (1H, d, J=8.3 Hz), 8.16 (1H, s), 7.99 (1H, bs), 7.46 (1H, dd, J=8.3, 1.8 Hz), 7.34 (1H, d, J=1.8 Hz), 4.38 (2H, t, J=5.0 Hz), 4.13-4.01 (1H, m), 3.37 (2H, t, J=5.0 Hz), 1.43 (3H, s), 1.41 (3H, s).

Workup

  1. temperatureheating
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. custompurified twice by flash chromatography (SiO2, gradient 50 to 75% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-8bf9cff293b842418c2ec3842e0f1b69
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

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