Cesium carbonate → HCID 68095362, compound

HRID 1502394Notes

Reaction equation

HRID 1502394 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[CH:6]=[CH:5]2.[CH:19]1([C:22]([NH2:24])=[O:23])[CH2:21][CH2:20]1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][N:11]=[C:2]([NH:24][C:22]([CH:19]3[CH2:21][CH2:20]3)=[O:23])[CH:3]=2)[N:8]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86674962HCID 86674962, compound

Product 1

HCID 68095362HCID 68095362, compoundYield 23.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-chloro-2-(2-chlorophenyl)-1,7-naphthyridine (50 mg, 0.2 mmol), cyclopropanecarboxamide (27 mg, 0.32 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (16 mg, 0.03 mmol), palladium acetate (4 mg, 0.02 mmol), and cesium carbonate (118 mg, 0.36 mmol) in 1,4-dioxane (1 mL) was heated at 90° C. for 3 hours. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (15 mg, 20%). 1H NMR (400 MHz, CDCl3) δ 9.28 (s, 1H), 8.58 (s, 1H), 8.28 (s, 1H), 8.16 (d, J=8.6 Hz, 1H), 7.90 (d, J=8.6 Hz, 1H), 7.71 (m, 1H), 7.53 (m, 1H), 7.42 (m, 2H), 1.64 (m, 1H), 1.21-1.14 (m, 2H), 1.01-0.91 (m, 2H). LCMS (Method E): RT=4.970 min, M+H+=324.1.

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

Sources & evidence

ORD record
ord-30121792e3ab4956a97af3f9ae89b022
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

Loading…