Dichloromethane → HCID 178487943、化合物

HRID 245676ノート

反応式

HRID 245676 の反応式
Br[C:2]1[N:3]=[C:4]([C@H:12]2[CH2:17][CH2:16][C@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([CH3:11])[C:6]=12.[CH3:25][O:26][C:27]1[CH:35]=[CH:34][CH:33]=[C:32]2[C:28]=1[CH:29]=[C:30]([C:37]([NH:39][C:40]1[CH:45]=[CH:44][C:43](B3OC(C)(C)C(C)(C)O3)=[CH:42][C:41]=1[O:55][CH3:56])=[O:38])[N:31]2[CH3:36].C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:25][O:26][C:27]1[CH:35]=[CH:34][CH:33]=[C:32]2[C:28]=1[CH:29]=[C:30]([C:37]([NH:39][C:40]1[CH:45]=[CH:44][C:43]([C:2]3[N:3]=[C:4]([C@H:12]4[CH2:17][CH2:16][C@H:15]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[CH2:14][CH2:13]4)[N:5]4[CH:10]=[CH:9][N:8]=[C:7]([CH3:11])[C:6]=34)=[CH:42][C:41]=1[O:55][CH3:56])=[O:38])[N:31]2[CH3:36]

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 673656514-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamideHCID 178432912HCID 178432912、化合物

生成物 1

HCID 178487943HCID 178487943、化合物収率 31.8%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a stirred suspension of 1-bromo-8-methyl-3-((trans)-4-(4-methylpiperazin-1-yl)cyclohexyl)imidazo[1,5-a]pyrazine (1.04 g) and 4-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide (2.227 mmol, 0.972 g) in dioxane (18 mL) and 2 M aqueous potassium carbonate (10.6 mmol, 5.3 mL) under a nitrogen atmosphere was added 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride, complex with dichloromethane (0.212 mmol, 0.171 g) and the reaction mixture was heated by a preheated oil bath at 100° C. After two hours the reaction mixture was cooled to room temperature, water added and extracted with dichloromethane/methanol 9/1. The organic layer was separated and the water layer was extracted again with dichloromethane/methanol 9/1. The combined organic layers were washed with brine and dried (sodium sulfate) and evaporated to dryness to afford crude sample which was purified using column chromatography (silica gel; dichloromethane/methanol gradient (0 to 15% methanol)). Trituration with ethanol afforded 4-methoxy-N-(2-methoxy-4-(8-methyl-3-((trans)-4-(4-methylpiperazin-1-yl)cyclohexyl)imidazo[1,5-a]pyrazin-1-yl)phenyl)-1-methyl-1H-indole-2-carboxamide (0.44 g).

後処理

  1. temperatureAfter two hours the reaction mixture was cooled to room temperature
  2. extractionextracted with dichloromethane/methanol 9/1
  3. customThe organic layer was separated
  4. extractionthe water layer was extracted again with dichloromethane/methanol 9/1
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. customevaporated to dryness
  8. customto afford crude sample which
  9. customwas purified

出典と根拠

ORDレコード
ord-6a11e224b0f844e68512935309438bc0
出典データセット
uspto-grants-2014_02
特許番号
US08658794B2

反応ノート

読み込み中…