Cesium carbonate → 6-(4-fluorophenyl)-7-methoxy-4-[[4-(piperidin-1-ylmethyl)anilino]methylidene]isoquinoline-1,3-dione

HRID 2236717Notes

Reaction equation

HRID 2236717 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[NH:7][C:6](=[O:15])[C:5]2=[CH:16][NH:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:20][CH:19]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>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.C(Cl)(Cl)Cl.[Pd].[Pd].CN(C)C=O>[F:31][C:32]1[CH:37]=[CH:36][C:35]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][C:11]=2[O:12][CH3:13])[C:8](=[O:14])[NH:7][C:6](=[O:15])[C:5]3=[CH:16][NH:17][C:18]2[CH:19]=[CH:20][C:21]([CH2:24][N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[CH:22][CH:23]=2)=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2856454-Fluorophenylboronic acidHCID 178486407HCID 178486407, compound

Product 1

HCID 1784864116-(4-fluorophenyl)-7-methoxy-4-[[4-(piperidin-1-ylmethyl)anilino]methylidene]isoquinoline-1,3-dioneYield 49.2%

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-Bromo-7-methoxy-4-[(4-piperidin-1-ylmethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione (272 mg, 0.578 mmole), N,N-dimethylformamide (2 mL), 4-fluorophenylboronic acid (202 mg, 1.44 mmole), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (78 mg, 0.075 mmole), tri(t-butyl)phosphine (28 mg, 0.138 mmole) and cesium carbonate (377 mg, 1.16 mmole) is stirred and heated at 110° C. for one hour, cooled in the refrigerator. The reaction mixture is evaporated to dryness, taken up in 5% methanol in chlororform and passed through a short pad of Florisil eluting with 5% methanol in chloroform. The eluate is evaporated in vacuo and treated with acetonitrile, filtered and dried to give a yellow-brown solid 138 mg (48%), mp 227-230° C.; MS (ESI): m/z 486.2 (M+H).

Workup

  1. temperaturecooled in the refrigerator
  2. customThe reaction mixture is evaporated to dryness
  3. customThe eluate is evaporated in vacuo
  4. additiontreated with acetonitrile
  5. filtrationfiltered
  6. customdried

Sources & evidence

ORD record
ord-b908b4e23ff9443c8dbef02b1ce47309
Source dataset
uspto-grants-2010_05
Patent number
US07713994B2

Reaction notes

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