Potassium Carbonate → MCH-1 antagonist 1

HRID 2390429Notes

Reaction equation

HRID 2390429 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.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][NH:29][C:28](=[O:32])[CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.N[C@@H]1CCCC[C@H]1N.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C(Cl)Cl.[Cu]I>[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][N:29]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[N:6]=[CH:5]3)[C:28](=[O:32])[CH:27]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 576255415-Bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazole

Product 1

HCID 24857598MCH-1 antagonist 1Yield 7.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of 5-bromo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazole (0.21 g, 0.70 mmol) in 1,4-dioxane (10 mL) stirred under nitrogen was treated sequentially with 4-(benzyloxy)pyridin-2(1H)-one (0.14 g, 0.70 mmol), trans-1,2-diaminocyclohexane (0.03 mL, 0.2 mmol), CuI (28 mg, 0.15 mmol) and K2CO3 (0.19 g, 1.4 mmol). After stirring overnight at 110° C., the mixture was allowed to cool to room temperature, diluted with CH2Cl2, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 95:5 to 90:10 gave the title compound (21 mg, 7%) as an off-white powder: 1H NMR (500 MHz, DMSO-d6) δ 8.03 (s, 1H), 7.66 (d, J=1.4 Hz, 1H), 7.53 (d, J=8.8 Hz, 1H), 7.43-7.36 (m, 6H), 7.28 (d, J=7.5 Hz, 1H), 6.09-6.06 (m, 2H), 5.06 (s, 2H), 4.58-4.55 (m, 2H), 3.03 (br s, 2H), 2.61 (br s, 4H), 1.81 (br s, 4H); ESI MS m/z 415 [M+H]+.

Workup

  1. stirringAfter stirring overnight at 110° C.
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 95:5 to 90:10

Sources & evidence

ORD record
ord-015736ccc5824d3bb7ac02990c224cd2
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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