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Trimethylamine → 2-(2-fluoro-phenyl)-4-(5-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-pyridin-3-yl)-[1,8]naphthyridine

HRID 1914953
ノート
印刷プレビュー

反応式

HRID 1914953 の反応式
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[O:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[O:31][CH2:32][CH2:33][N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1.CC1(C)C(C)(C)OB(C2C=NNC=2)O1.ClC1C=CC(F)=C(C2C=C(C3C=NC=C(C4C=NN(CCN5CCCC5)C=4)C=3)C3C(=NC=CC=3)N=2)C=1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C>COCCOC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:10]1[CH:9]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:37]3[CH:36]=[N:35][N:34]([CH2:33][CH2:32][O:31][CH:26]4[CH2:27][CH2:28][CH2:29][CH2:30][O:25]4)[CH:38]=3)[CH:3]=2)[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1
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

9

反応物 6

HCID 1146TrimethylamineHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 18407952Tripotassium phosphate trihydrateHCID 53344959HCID 53344959、化合物HCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 682645484-(5-Bromo-pyridin-3-yl)-2-(2-fluoro-phenyl)-[1,8]naphthyridine

生成物 1

HCID 673805632-(2-fluoro-phenyl)-4-(5-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-pyridin-3-yl)-[1,8]naphthyridine

試薬・触媒・溶媒 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

A slurry of 380 mg (1.00 mmol) 4-(5-bromo-pyridin-3-yl)-2-(2-fluoro-phenyl)-[1,8]naphthyridine, 354 mg (1.10 mmol) 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (prepared from 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole and 2-(2-bromo-ethoxy)-tetrahydro-pyran (in analogy to example 10) and 425 mg (2.00 mmol) tri-potassium-phosphate-trihydrate in 3 ml 1,2-dimethoxyethane was heated to 85° C. under nitrogen. Then 35.1 mg (0.05 mmol) bis-(triphenylphosphine)-palladium(II)-chloride and 14 μl trimethylamine were added. The reaction mixture was stirred for 16 hours at 85° C. The reaction mixture was cooled to room temperature and partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding yielding 2-(2-fluoro-phenyl)-4-(5-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-pyridin-3-yl)-[1,8]naphthyridine as yellow solid; HPLC-MS: 2.13 min, [M+H] 496.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between water and dichloromethane
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. customevaporated
  5. customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent
  6. customyielding

出典と根拠

ORDレコード
ord-93862f2cadbd49ef9c8f1cdc0850b62f
出典データセット
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08614226B2

反応ノート

読み込み中…

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