Potassium Carbonate → 2-Chloro-4,4-difluoro-1'-[[1-(3-methoxy-2-pyridyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]

HRID 1517609ノート

反応式

HRID 1517609 の反応式
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:24])([F:23])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][NH:17][CH:18]=1)[CH2:9][CH2:8]3.C(=O)([O-])[O-].[K+].[K+].I[C:32]1[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[CH:34][N:33]=1.CN[C@@H]1CCCC[C@H]1NC>[Cu]I.C1(C)C=CC=CC=1>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:23])([F:24])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][N:17]([C:32]2[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[CH:34][N:33]=2)[CH:18]=1)[CH2:9][CH2:8]3

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 8171732-Iodo-3-methoxypyridineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178434546HCID 178434546、化合物

生成物 1

HCID 582686102-Chloro-4,4-difluoro-1'-[[1-(3-methoxy-2-pyridyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]収率 54.1%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 1140Toluene溶媒

実験手順

To a screw-cap test tube are added copper(I) iodide (23.74 mg, 0.125 mmol), 2-chloro-4,4-difluoro-1′-[(3-methyl-1H-pyrazol-4-yl)methyl]spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (233.00 mg, 0.623 mmol), potassium carbonate (182.71 mg, 1.31 mmol), toluene (2 mL) (previously bubbled with nitrogen for 20 min) and a stir bar. The reaction mixture is bubbled with nitrogen for 20 minutes and then 2-iodo-3-methoxypyridine (302.01 mg, 1.25 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (39.31 mL, 0.25 mmol) are added. The reaction tube is quickly sealed (caution: build-up of pressure possible; use a safety shield) and immersed in a preheated oil bath at 110° C. for 24 hours with the aid of a magnetic stirrer. Then, the mixture is poured on SCX column (25 g) and eluted with methanol and then 2N solution of ammonia in methanol. The basic fraction is concentrated and the resulting residue is purified by basic-HPLC to give 162 mg of the title compound. MS (m/z): 481 (M+1).

後処理

  1. custompreviously bubbled with nitrogen for 20 min) and a stir bar
  2. customThe reaction mixture is bubbled with nitrogen for 20 minutes
  3. customThe reaction tube is quickly sealed (caution
  4. additionThen, the mixture is poured on SCX column (25 g)
  5. washeluted with methanol
  6. concentrationThe basic fraction is concentrated
  7. customthe resulting residue is purified by basic-HPLC

出典と根拠

ORDレコード
ord-25627668f3ed4a23adb05f91132f636d
出典データセット
uspto-grants-2012_07
特許番号
US08232289B2

反応ノート

読み込み中…