Potassium Carbonate → MCH-1 antagonist 1

HRID 2387474노트

반응식

HRID 2387474 반응식
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

참가 물질

8

반응물 4

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

생성물 1

HCID 24857598MCH-1 antagonist 1수율 7.2%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-30cbcb04b33f43b1a19f3108b81e250e
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268868B2

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