4-Bromopyridinium chloride → 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

HRID 1776392ノート

反応式

HRID 1776392 の反応式
[CH3:1][O:2][C:3]1[C:4]([NH2:27])=[N:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[N:10]=2)=[N:7][CH:8]=1.Cl.Br[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.CC([O-])(C)C.[Na+]>CN(C=O)C.ClCCl.C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:1][O:2][C:3]1[C:4]([NH:27][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)=[N:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[N:10]=2)=[N:7][CH:8]=1

参加物

7

反応物 3

HCID 881004-Bromopyridinium chloride2 回HCID 23676156Sodium t-butoxide2 回HCID 867324165-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine

生成物 1

HCID 867324175-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

試薬・触媒・溶媒 3

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladium触媒2 回HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

205 mg of 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine (1-4-1, 0.568 mmol, 1 eq.), 121.6 mg of 4-bromopyridine hydrochloride (1:1) (0.625 mmol. 1.1 eq.), 136.5 mg of sodium 2-methylpropan-2-olate (1.42 mmol, 2.5 eq.), 106.2 mg of 1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.171 mmol, 0.3 eq.) and 52.0 mg of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) (0.057 mmol, 0.1 eq.) were suspended in 3 ml of dry DMF under nitrogen atmosphere. The reaction mixture was stirred for two days at 100° C. 122 mg of 4-bromopyridine hydrochloride (1:1) (0.625 mmol. 1.1 eq.), 137 mg of sodium 2-methylpropan-2-olate (1.42 mmol, 2.5 eq.), 106 mg of 1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.171 mmol, 0.3 eq.) and 52.0 mg of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) (0.057 mmol, 0.1 eq.) were added and stirred for further 24 hours. The mixture was cooled down to room temperature, diluted with 10 ml dichloromethane and filtered off. The filtrate was concentrated in vacuo. The residue was purified by flash chromatography to yield 126 mg (0.23 mmol, 81%) of the analytically pure target compound.

後処理

  1. stirringstirred for further 24 hours
  2. temperatureThe mixture was cooled down to room temperature
  3. filtrationfiltered off
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by flash chromatography
  6. customto yield 126 mg (0.23 mmol, 81%) of the analytically pure target compound

出典と根拠

ORDレコード
ord-090713e78eb3411ab218e958c45e3687
出典データセット
uspto-grants-2016_02
特許番号
US09265763B2

反応ノート

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