Acetic Acid → [2-Amino-6-(2-{[ethyl-(2-hydroxyethyl)amino]methyl}-4-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

HRID 1631117노트

반응식

HRID 1631117 반응식
[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.[CH2:32]([NH:34][CH2:35][CH2:36][OH:37])[CH3:33].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:34]([CH2:32][CH3:33])[CH2:35][CH2:36][OH:37])[CH:8]=2)[N:3]=1

참가 물질

8

반응물 4

HCID 176Acetic AcidHCID 80722-(Ethylamino)ethanolHCID 5049666Sodium triacetoxyborohydrideHCID 871741022-[2-Amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-5-fluorobenzaldehyde

생성물 1

HCID 56943511[2-Amino-6-(2-{[ethyl-(2-hydroxyethyl)amino]methyl}-4-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
60 °C

실험 절차

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. 57 μl of 2-(ethylamino)ethanol and 28 μl of glacial acetic acid are added, and the mixture is stirred at 60° C. for 6 h. After cooling to 25° C., 216 mg of sodium triacetoxyborohydride are added, and the mixture is 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).

후처리

  1. temperatureAfter cooling to 25° C.
  2. stirringthe mixture is stirred 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)

출처 및 근거

ORD 기록
ord-dee2abed291244a6ae71d5e3bb763ce6
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791129B2

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