Cesium carbonate → HCID 25017033, compound

HRID 422073Notes

Reaction equation

HRID 422073 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)[N:6]=[CH:5]2.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[O:33][C:32]3[CH:31]=[CH:30][NH:29][C:28](=[O:34])[C:27]=3[CH:26]=2)=[CH:21][CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC>CN1C(=O)CCC1.[Cu]I>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[O:33][C:32]3[CH:31]=[CH:30][N:29]([C:2]4[CH:3]=[C:4]5[C:8](=[CH:9][CH:10]=4)[N:7]([CH2:11][CH2:12][N:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)[N:6]=[CH:5]5)[C:28](=[O:34])[C:27]=3[CH:26]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 576255415-Bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazoleHCID 580155582-(4-chlorophenyl)-5H-furo[3,2-c]pyridine-4-one

Product 1

HCID 25017033HCID 25017033, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 5-bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazole (0.349 g, 1.18 mmol) in NMP (3.3 mL) was added to 2-(4-chlorophenyl)-5H-furo[3,2-c]pyridine-4-one (0.347 g, 1.41 mmol), Cs2CO3 (0.768 g, 2.36 mmol), trans-1,2-bis(methylamino) cyclohexane (0.035 mL, 0.236 mmol) and CuI (0.269 g, 1.41 mmol) and deoxygenated with argon for 30 minutes. After stirring at 110° C. for 48 hours, the reaction mixture was cooled and diluted with CH2Cl2 (10 mL) and water (10 mL) and extracted with CH2Cl2 (4×50 mL). The organics were filtered through Celite and concentrated. Purification by flash chromatography (silica gel, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) followed by preparative HPLC (Phenomenex Luna C18 (2), 250.0×50.0 mm, 10 micron, H2O with 0.05% trifluoroacetic acid (TFA) and CH3CN with 0.05% TFA) yielded the title compound (7.5 mg, 13%) as a light yellow solid: ESI MS m/z 459 [M+H]+.

Workup

  1. customdeoxygenated with argon for 30 minutes
  2. temperaturethe reaction mixture was cooled
  3. additiondiluted with CH2Cl2 (10 mL) and water (10 mL)
  4. extractionextracted with CH2Cl2 (4×50 mL)
  5. filtrationThe organics were filtered through Celite
  6. concentrationconcentrated
  7. customPurification by flash chromatography (silica gel, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100)

Sources & evidence

ORD record
ord-7e73e1a574cc4bbb909a2ad4ac8dde55
Source dataset
uspto-grants-2012_01
Patent number
US08101632B2

Reaction notes

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