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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
ノート
印刷プレビュー

反応式

HRID 1631174 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒2 回

反応条件

温度
0 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-1161e325794642478c22d1d764aef42e
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08791129B2

反応ノート

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