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Cesium carbonate → ethyl 4-({2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridine-3-carboxylate

HRID 1776443
ノート
印刷プレビュー

反応式

HRID 1776443 の反応式
[CH2:1]([O:3][C:4]1[CH:28]=[C:27]([F:29])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH2:24])[C:21]([O:25][CH3:26])=[CH:20][N:19]=3)=[N:10]2)=[C:6]([F:30])[CH:5]=1)[CH3:2].Cl[C:32]1[C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:36][N:35]=[CH:34][CH:33]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([F:30])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH:24][C:32]4[CH:33]=[CH:34][N:35]=[CH:36][C:37]=4[C:38]([O:40][CH2:41][CH3:42])=[O:39])[C:21]([O:25][CH3:26])=[CH:20][N:19]=3)=[N:10]2)=[C:27]([F:29])[CH:28]=1)[CH3:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 14116704Ethyl 4-chloropyridine-3-carboxylateHCID 867324712-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine

生成物 1

HCID 86732470ethyl 4-({2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridine-3-carboxylate

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
105 °C

実験手順

150 mg of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine (1-4-3, 0.365 mmol, 1.0 eq.), 89 mg of commercial ethyl 4-chloronicotinate (0.401 mmol, 1.1 eq.), 31.6 mg of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.055 mmol, 0.15 eq.), 356 mg of caesium carbonate (1.09 mmol, 3.0 eq.) and 8.2 mg of palladium diacetate (0.036 mmol, 0.1 eq.) were suspended in 4.7 mL of dry dioxane and stirred under nitrogen atmosphere at 105° C. bath temperature for 3 h. Solids were filtered off, washed with dioxane and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography yielding 77 mg from which only 15.7 mg were further purified by crystallization from THF to yield 3.1 mg (0.01 mmol, 1.44%) of analytically pure target compound.

後処理

  1. filtrationSolids were filtered off
  2. washwashed with dioxane
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography
  5. customyielding 77 mg from which only 15.7 mg
  6. customwere further purified by crystallization from THF
  7. customto yield 3.1 mg (0.01 mmol, 1.44%) of analytically pure target compound

出典と根拠

ORDレコード
ord-5f868cad9cd8404e87a93e98f64fa04a
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09265763B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート