Potassium Carbonate → 4-(7-(1-methyl-1H-pyrrol-3-yl)-8-(piperidin-4-yloxy)quinazolin-2-ylamino)benzenesulfonamide

HRID 2079622ノート

反応式

HRID 2079622 の反応式
C([O-])([O-])=O.[K+].[K+].Br[C:8]1[C:17]([O:18][CH:19]2[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]2)=[C:16]2[C:11]([CH:12]=[N:13][C:14]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([S:39](=[O:42])(=[O:41])[NH2:40])=[CH:35][CH:34]=3)=[N:15]2)=[CH:10][CH:9]=1.[CH3:43][N:44]1[CH:48]=[CH:47][C:46](B2OC(C)(C)C(C)(C)O2)=[CH:45]1>COCCOC.[Pd]>[CH3:43][N:44]1[CH:48]=[CH:47][C:46]([C:8]2[C:17]([O:18][CH:19]3[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]3)=[C:16]3[C:11]([CH:12]=[N:13][C:14]([NH:32][C:33]4[CH:34]=[CH:35][C:36]([S:39]([NH2:40])(=[O:41])=[O:42])=[CH:37][CH:38]=4)=[N:15]3)=[CH:10][CH:9]=2)=[CH:45]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 532171481-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrroleHCID 59199265Tert-butyl 4-(7-bromo-2-(4-sulfamoylphenylamino)quinazolin-8-yloxy)piperidine-1-carboxylate

生成物 1

HCID 591992634-(7-(1-methyl-1H-pyrrol-3-yl)-8-(piperidin-4-yloxy)quinazolin-2-ylamino)benzenesulfonamide収率 22.9%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
92.5 °C

実験手順

A 2M solution of K2CO3 (180 μL) was added to a mixture of tert-butyl 4-(7-bromo-2-(4-sulfamoylphenylamino)quinazolin-8-yloxy)piperidine-1-carboxylate (18 mg, 0.031 mmole), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (20 mg, 0.093 mmole) and palladium (4 mg, 0.005 mmole) in DME (0.6 mL). The reaction was sparged with argon, sealed and heated at 90-95° C. with stirring. After 90 minutes, LCMS showed that the reaction had reached completion. The Boc group was removed by adding 4M HCl (1.5 mL) in dioxane to the cooled reaction mixture. After 2 hours, the reaction was complete by LCMS. The reaction was filtered, evaporated, dissolved in DMSO (1 mL) and purified by prep. HPLC to give 3.4 mg of the pure product as a TFA salt.

後処理

  1. customThe reaction was sparged with argon
  2. customsealed
  3. customThe Boc group was removed
  4. additionby adding 4M HCl (1.5 mL) in dioxane
  5. customto the cooled reaction mixture
  6. waitAfter 2 hours
  7. filtrationThe reaction was filtered
  8. customevaporated
  9. dissolutiondissolved in DMSO (1 mL)
  10. custompurified by prep

出典と根拠

ORDレコード
ord-76489bad23784b35bc2f2a6b0e044c85
出典データセット
uspto-grants-2011_04
特許番号
US07932262B2

反応ノート

読み込み中…