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Triethylamine → [3-(4-{5-[2-(5-Chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-propyl]-dimethyl-amine

HRID 1914951
ノート
印刷プレビュー

反応式

HRID 1914951 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]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=3[F:25])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:26][N:27]([CH3:45])[CH2:28][CH2:29][CH2:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(N(CC)CC)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>[Cl:24][C:22]1[CH:21]=[CH:20][C:19]([F:25])=[C:18]([C:10]2[CH:9]=[C:8]([C:4]3[CH:3]=[C:2]([C:34]4[CH:33]=[N:32][N:31]([CH2:30][CH2:29][CH2:28][N:27]([CH3:26])[CH3:45])[CH:35]=4)[CH:7]=[N:6][CH:5]=3)[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:23]=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

7

反応物 4

HCID 8471TriethylamineHCID 6420914N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanamineHCID 18407952Tripotassium phosphate trihydrateHCID 673643764-(5-Bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine

生成物 1

HCID 53345070[3-(4-{5-[2-(5-Chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-propyl]-dimethyl-amine

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 500 mg (1.21 mmol) 4-(5-bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine, 370 mg (1.33 mmol) dimethyl-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]propyl}-amine and 512 mg (2.41 mmol) tri-potassium-phosphate-trihydrate in 5 ml 1,2-dimethoxyethane is heated to 85° C. under nitrogen. Then 42.3 mg (0.06 mmol) bis-(triphenylphosphine)-palladium(II)-chloride and 17 μl triethylamine were added. The reaction mixture was stirred for 2 hours at 85° C. The reaction mixture was partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate and evaporated. The residue was crystallized from acetonitrile yielding [3-(4-{5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-3-yl}-pyrazol-1-yl)-propyl]-dimethyl-amine as light grey crystals; HPLC-MS: 1.64 min, [M+H] 487. 1H NMR (500 MHz, DMSO) δ=9.21 (dd, J=4.1, 1.8, 1H), 9.05 (d, J=2.1, 1H), 8.63 (d, J=2.0, 1H), 8.41 (s, 1H), 8.37 (dd, J=8.4, 1.8, 1H), 8.28 (t, J=2.1, 1H), 8.18 (dd, J=6.6, 2.8, 1H), 8.10 (m, 2H), 7.72 (dd, J=8.4, 4.2, 1H), 7.68 (ddd, J=8.7, 4.0, 3.0, 1H), 7.52 (dd, J=10.6, 8.9, 1H), 4.16 (t, J=7.0, 2H), 2.22 (t, J=6.7, 2H), 2.14 (s, 6H), 1.94 (p, J=7.0, 2H).

後処理

  1. customThe reaction mixture was partitioned between water and dichloromethane
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. customevaporated
  4. customThe residue was crystallized from acetonitrile

出典と根拠

ORDレコード
ord-72d813cfc6f34e38bfcf3aea648e9bf4
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…

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