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Tributylphosphine → 4-(4-Chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline

HRID 453995
ノート
印刷プレビュー

反応式

HRID 453995 の反応式
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.C(P(CCCC)CCCC)CCC.[O:36]=[S:37]1(=[O:47])[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][CH2:45]O)[CH2:39][CH2:38]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>ClCCl.CCOCC>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:45][CH2:44][CH2:43][N:40]4[CH2:39][CH2:38][S:37](=[O:47])(=[O:36])[CH2:42][CH2:41]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 114354734-(3-Hydroxypropyl)thiomorpholine 1,1-DioxideHCID 1356162044-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 219359994-(4-Chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline収率 70%

試薬・触媒・溶媒

2
HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

実験手順

4-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (5.0 g, 15.6 mmol) was suspended in dichloromethane (150 ml) and tributylphosphine (11.1 ml, 44.6 mmol) was added followed by stirring at ambient temperature for 30 minutes. To this mixture was added 3-(1,1-dioxothiomorpholino)-1-propanol (4.2 g, 21.8 mmol) followed by the addition of 1,1′-(azodicarbonyl)dipiperidine (11.7 g, 46.4 mmol) in portions. The mixture was stirred at ambient temperature overnight then diluted with ether (300 ml) and the precipitate was removed by filtration. The residue was chromatographed on silica eluting with dichloromethane and methanol (95/5). The relevant fractions were combined and evaporated to give a solid which was triturated with ethyl acetate filtered and dried to give 4-(4-chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline (5.4 g, 70%).

後処理

  1. stirringThe mixture was stirred at ambient temperature overnight
  2. customthe precipitate was removed by filtration
  3. customThe residue was chromatographed on silica eluting with dichloromethane and methanol (95/5)
  4. customevaporated
  5. customto give a solid which
  6. customwas triturated with ethyl acetate
  7. filtrationfiltered
  8. customdried

出典と根拠

ORDレコード
ord-177561d139434939a020630c8378a071
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08492560B2

反応ノート

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