Cesium carbonate → HCID 56925086, compound

HRID 1811178Notes

Reaction equation

HRID 1811178 reaction equation
Br[C:2]1[C:3]([CH3:28])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([C:21]([OH:24])([CH3:23])[CH3:22])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:25]([NH2:27])=[O:26])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:29][O:30][C:31]1[CH2:35][NH:34][C:33](=[O:36])[CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:24][C:21]([C:16]1[CH:15]=[C:14]2[C:19]([C:20]3[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([N:34]5[CH2:35][C:31]([O:30][CH3:29])=[CH:32][C:33]5=[O:36])[C:3]=4[CH3:28])=[CH:9][CH:10]=[C:11]([C:25]([NH2:27])=[O:26])[C:12]=3[NH:13]2)=[CH:18][CH:17]=1)([CH3:22])[CH3:23]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5747694-methoxy-2,5-dihydro-1H-pyrrol-2-oneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 66606710HCID 66606710, compound2×

Product 1

HCID 56925086HCID 56925086, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(3-bromo-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (Intermediate 81-25, 70 mg, 0.160 mmol), 4-methoxy-1H-pyrrol-2(5H)-one (362 mg, 3.20 mmol), cesium carbonate (78 mg, 0.24 mmol), tris(dibenzylideneacetone)dipalladium (14.7 mg, 0.016 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos, 27.8 mg, 0.048 mmol) in 1,4-dioxane (2 mL) was purged with nitrogen and heated via microwave irradiation in a sealed tube at 100° C. for 1 h. The mixture was diluted with DCM, washed with NaHCO3 (aq), dried and concentrated. The residue was purified by preparative HPLC, and the appropriate effluent fractions were treated with NaHCO3 (aq) and extracted with DCM. The combined organic phases were washed with water, dried and concentrated to provide as a white solid (20 mg, 27%). 1H NMR (400 MHz, methanol-d4) δ 7.91 (1H, d, J=7.70 Hz), 7.73 (1H, d, J=0.88 Hz), 7.39-7.46 (2H, m), 7.31-7.34 (1H, m), 7.09 (1H, dd, J=8.47, 1.65 Hz), 7.01 (1H, d, J=7.70 Hz), 6.98 (1H, d, J=8.36 Hz), 5.29 (1H, s), 4.37-4.49 (2H, m), 3.91 (3H, s), 1.90 (3H, s), 1.58 (3H, s), 1.57 (3H, s). Mass spectrum m/z 492.0 (M+Na)+.

Workup

  1. customwas purged with nitrogen
  2. additionThe mixture was diluted with DCM
  3. washwashed with NaHCO3 (aq)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC
  7. additionthe appropriate effluent fractions were treated with NaHCO3 (aq)
  8. extractionextracted with DCM
  9. washThe combined organic phases were washed with water
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-05c645b2c0f6425a8e404aee522d562c
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

Loading…