Acetic Acid → {2-Amino-6-[4-fluoro-2-(4-methylpiperazin-1-ylmethyl)phenyl]quinazolin-4-yl}-(1,3-dihydroisoindol-2-yl)methanone

HRID 1631141ノート

反応式

HRID 1631141 の反応式
[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:24]=3[CH:25]=O)[CH:8]=2)[N:3]=1.[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O1CCCC1.O>[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:24]=3[CH2:25][N:36]3[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]3)[CH:8]=2)[N:3]=1

参加物

8

反応物 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 871741022-[2-Amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-5-fluorobenzaldehyde

生成物 1

HCID 56943213{2-Amino-6-[4-fluoro-2-(4-methylpiperazin-1-ylmethyl)phenyl]quinazolin-4-yl}-(1,3-dihydroisoindol-2-yl)methanone

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

114 mg of 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-5-fluorobenzaldehyde are dissolved in 2 ml of 1,2-dichloroethane and 2 ml of tetrahydrofuran. 97 μl of 1-methylpiperazine and 50 μl of glacial acetic acid are added, and the mixture is stirred at 60° C. for 6 h. After cooling to 25° C., 195 mg of sodium triacetoxyborohydride are added and stirred at 25° C. for a further 12 h. The mixture is poured into water, extracted three times with dichloromethane, and the combined organic phases are dried over sodium sulfate. After filtration, the filtrate is evaporated to dryness and purified by chromatography (reversed phase HPLC).

後処理

  1. temperatureAfter cooling to 25° C.
  2. stirringstirred at 25° C. for a further 12 h
  3. extractionextracted three times with dichloromethane
  4. dry with materialthe combined organic phases are dried over sodium sulfate
  5. filtrationAfter filtration
  6. customthe filtrate is evaporated to dryness
  7. custompurified by chromatography (reversed phase HPLC)

出典と根拠

ORDレコード
ord-181684fb29494935b42b5c5a2f90d6bb
出典データセット
uspto-grants-2014_07
特許番号
US08791129B2

反応ノート

読み込み中…