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Hydrochloric Acid → 2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (2-dimethylaminoethyl)carbamate

HRID 1631174
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HRID 1631174 반응식
[C:1]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)(N1C=CN=C1)=[O:2].[NH2:13][C:14]1[N:23]=[C:22]([C:24]([N:26]2[CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27]2)=[O:25])[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:35]3[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=3[CH2:43][OH:44])[CH:20]=2)[N:15]=1.[CH3:45]N(C)CCN.Cl.C(=O)(O)[O-]>N1C=CC=CC=1>[CH3:45][N:10]([CH3:9])[CH2:11][CH2:12][NH:8][C:1](=[O:2])[O:44][CH2:43][C:36]1[CH:37]=[C:38]([F:42])[C:39]([F:41])=[CH:40][C:35]=1[C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][CH:18]=1)[N:15]=[C:14]([NH2:13])[N:23]=[C:22]2[C:24]([N:26]1[CH2:27][C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:34]1)=[O:25]
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참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 769Bicarbonate IonHCID 66053N,N-DimethylethylenediamineHCID 682631,1'-CarbonyldiimidazoleHCID 56943446[2-Amino-6-[4,5-difluoro-2-(hydroxymethyl)phenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

생성물 1

HCID 56944456
2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (2-dimethylaminoethyl)carbamate

시약·촉매·용매 1

HCID 1049Pyridine용매2회

반응 조건

온도
0 °C

실험 절차

400 mg of 1,1′-carbonyldiimidazole are dissolved in 10 ml of pyridine and cooled to 0° C. A solution of 1.0 g of [2-amino-6-(4,5-difluoro-2-hydroxymethylphenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone dissolved in 10 ml of pyridine is added. The mixture is subsequently stirred at 0° C. for 2 h and at 25° C. for 2 h. 300 μl of N,N-dimethylethylenediamine are then added, and the mixture is stirred at 25° C. for a further 18 h. The mixture is added to 250 ml of 1 N HCl, neutralised using bicarbonate solution and washed 3 times with 150 ml of dichloromethane each time. The organic phases are washed twice with 50 ml of water each time, dried over sodium sulfate, filtered and evaporated to dryness in vacuo. The residue is dissolved in 1 ml of dimethyl sulfoxide and purified by chromatography (reversed phase).

후처리

  1. additionis added
  2. stirringthe mixture is stirred at 25° C. for a further 18 h
  3. washwashed 3 times with 150 ml of dichloromethane each time
  4. washThe organic phases are washed twice with 50 ml of water each time
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness in vacuo
  8. dissolutionThe residue is dissolved in 1 ml of dimethyl sulfoxide
  9. custompurified by chromatography (reversed phase)

출처 및 근거

ORD 기록
ord-1161e325794642478c22d1d764aef42e
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08791129B2

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