Potassium Carbonate → MCH-1 antagonist 1

HRID 2387474ノート

反応式

HRID 2387474 の反応式
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

参加物

8

反応物 4

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

生成物 1

HCID 24857598MCH-1 antagonist 1収率 7.2%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

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 m, 2H), 2.61 (br m, 4H), 1.81 (br m, 4H); ESI MS m/z 415 [M+H]+.

後処理

  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)

出典と根拠

ORDレコード
ord-30cbcb04b33f43b1a19f3108b81e250e
出典データセット
uspto-grants-2012_09
特許番号
US08268868B2

反応ノート

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