Cesium carbonate → 2-Phenyl-5-(1-(2-(pyrrolidine-1-yl)ethyl)-1H-indazol-5-yl)furo[3,2-c]pyridine-4(5H)-one

HRID 422071

Reaction equation

HRID 422071 reaction equation
I[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.[C:18]1([C:24]2[O:32][C:31]3[CH:30]=[CH:29][NH:28][C:27](=[O:33])[C:26]=3[CH:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+].N[C@@H]1CCCC[C@H]1N>CN1CCCC1=O.[Cu]I>[C:18]1([C:24]2[O:32][C:31]3[CH:30]=[CH:29][N:28]([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:27](=[O:33])[C:26]=3[CH:25]=2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 152726242-phenylfuro[3,2-c]pyridin-4(5H)-oneHCID 580155445-Iodo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazole

Product 1

HCID 248575972-Phenyl-5-(1-(2-(pyrrolidine-1-yl)ethyl)-1H-indazol-5-yl)furo[3,2-c]pyridine-4(5H)-oneYield 7.6%

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-iodo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazole (0.316 g, 0.923 mmol) in N-methylpyrrolidone (NMP) (2.7 mL) was added to 2-phenyl-5H-furo[3,2-c]pyridine-4-one (0.232 g, 1.10 mmol), Cs2CO3 (0.601 g, 1.84 mmol), trans-1,2-diaminocyclohexane (21.2 mL, 0.184 mmol) and CuI (0.210 g, 1.10 mmol) and deoxygenated with argon for 30 minutes. After stirring at 110° C. for 48 hours, the reaction mixture was cooled and diluted with MeOH (3 mL) and a solution of 7:1 MeOH/NH4OH (3 mL) and filtered through Celite. The filtrate was concentrated and then suspended with CH2Cl2 (20 mL) and water (20 mL) and extracted with CH2Cl2 (4×50 mL). The combined organics were dried (Na2SO4) and concentrated. Purification by flash chromatography (silica gel, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) yielded the title compound (29.6 mg, 7%) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.80 (d, J=7.5 Hz, 2H), 7.73 (d, J=2.0 Hz, 1H), 7.57 (d, J=9.0 Hz, 1H), 7.47-7.42 (m, 3H), 7.37-7.33 (m, 3H), 6.68 (d, J=7.5 Hz, 1H), 4.60 (t, J=7.0 Hz, 2H), 3.06 (br m, 2H), 2.62 (br m, 4H), 1.81 (br m, 4H); ESI MS m/z 425 [M+H]+; HPLC (Method A) 96.4% (AUC), tR=15.0 mm.

Workup

  1. customdeoxygenated with argon for 30 minutes
  2. temperaturethe reaction mixture was cooled
  3. additiondiluted with MeOH (3 mL)
  4. filtrationa solution of 7:1 MeOH/NH4OH (3 mL) and filtered through Celite
  5. concentrationThe filtrate was concentrated
  6. extractionextracted with CH2Cl2 (4×50 mL)
  7. dry with materialThe combined organics were dried (Na2SO4)
  8. concentrationconcentrated
  9. customPurification by flash chromatography (silica gel, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100)

Sources & evidence

ORD record
ord-4b7323da54394688a193dabd974fd32a
Source dataset
uspto-grants-2012_01
Patent number
US08101632B2

Linked notes

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