Water → 1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(1H-pyrazol-4-yl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618703ノート

反応式

HRID 1618703 の反応式
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[CH2:9][C:8]3([CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:5]2=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:42]2[CH:43]=[N:44][NH:45][CH:46]=2)O1.C([O-])([O-])=O.[Na+].[Na+].O>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([N:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:42]5[CH:43]=[N:44][NH:45][CH:46]=5)[CH:3]=4)[C:8]4([CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)[CH2:9]3)=[C:12]([CH3:28])[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[N:14]2)=[CH:19][CH:18]=1

参加物

7

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2 回HCID 672853616'-Bromo-1'-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

生成物 1

HCID 672850981'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(1H-pyrazol-4-yl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒2 回HCID 1140Toluene溶媒

反応条件

温度
140 °C

実験手順

A stirred solution of 6′-bromo-1′-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (25 mg, 0.049 mmol), 4,4,5,5-tetramethyl-2-(1H-pyrazol-4-yl)-1,3,2-dioxaborolane (9.60 mg, 0.049 mmol), PdCl2(PPh3)2 (3.5 mg, 4.95 μmol) and Na2CO3 (10.5 mg, 0.099 mmol) in toluene:water (2 mL:1 mL) was heated in the microwave for 2 h at 120° C. After this time PdCl2(PPh3)2 (5.0 mg) and 4,4,5,5-tetramethyl-2-(1H-pyrazol-4-yl)-1,3,2-dioxaborolane (9.60 mg, 0.049 mmol) was added and the reaction was heated in the microwave for 1 h at 140° C. After this time the reaction was partitioned between EtOAc (50 mL) and water (20 mL). The separated organic layer was dried with MgSO4, filtered and evaporated in vacuo. Reverse phase HPLC (10 to 60% acetonitrile:water) gave 1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(1H-pyrazol-4-yl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. Mass Spectrum (ESI) m/e=493.0 (M+1).

後処理

  1. customAfter this time the reaction was partitioned between EtOAc (50 mL) and water (20 mL)
  2. dry with materialThe separated organic layer was dried with MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo

出典と根拠

ORDレコード
ord-7c8a4d4be778407590cf16b102ca5210
出典データセット
uspto-grants-2014_07
特許番号
US08765940B2

反応ノート

読み込み中…