Triphenylphosphine → 4-(7-Azaindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline

HRID 916378ノート

反応式

HRID 916378 の反応式
N(C(OCC)=O)=NC(OCC)=O.[NH:13]1[C:21]2[C:16](=[CH:17][C:18]([O:22][C:23]3[C:32]4[C:27](=[CH:28][C:29]([O:34][CH3:35])=[C:30]([OH:33])[CH:31]=4)[N:26]=[CH:25][N:24]=3)=[CH:19][N:20]=2)[CH:15]=[CH:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:55][S:56]([N:59]1[CH2:64][CH2:63][N:62]([CH2:65][CH2:66][CH2:67]O)[CH2:61][CH2:60]1)(=[O:58])=[O:57]>CN(C=O)C>[NH:13]1[C:21]2[C:16](=[CH:17][C:18]([O:22][C:23]3[C:32]4[C:27](=[CH:28][C:29]([O:34][CH3:35])=[C:30]([O:33][CH2:67][CH2:66][CH2:65][N:62]5[CH2:63][CH2:64][N:59]([S:56]([CH3:55])(=[O:58])=[O:57])[CH2:60][CH2:61]5)[CH:31]=4)[N:26]=[CH:25][N:24]=3)=[CH:19][N:20]=2)[CH:15]=[CH:14]1

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 219360993-(4-Methylsulfonylpiperazin-1-yl)propan-1-olHCID 589602364-(7-Azaindol-5-yloxy)-6-hydroxy-7-methoxyquinazohne

生成物 1

HCID 98064454-(7-Azaindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline収率 40%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Diethyl azodicarboxylate (0.09 g, 0.518 mmol) was added dropwise to a solution of 4-(7-azaindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline (0.133 g, 0.432 mmol), triphenylphosphine (0.17 g, 0.647 mmol) and 3-(4-methylsulphonylpiperazin-1-yl)propan-1-ol (0.115 g, 0.519 mmol) in DMF (4 ml) and the mixture was stirred at ambient temperature for 1 hour. The volatiles were removed under vacuum and the residue was purified by column chromatography using increasingly polar mixtures of ethyl acetate and methylene chloride followed by methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The solid was then repurified by preparative LC/MS eluting with acetonitrile/water (containing 1% acetic acid). The fractions containing the expected product were combined and evaporated. The residue was dissolved in aqueous sodium hydrogen carbonate and methylene chloride. The organic phase was separated and dried over magnesium sulphate and evaporated. The residue was triturated under diethyl ether, filtered, washed with ether and dried under vacuum over P2O5 to give 4-(7-azaindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline (0.09, 40%).

後処理

  1. customThe volatiles were removed under vacuum
  2. customthe residue was purified by column chromatography
  3. temperatureusing increasingly polar mixtures of ethyl acetate and methylene chloride
  4. additionThe fractions containing the expected product
  5. customevaporated
  6. customThe solid was then repurified by preparative LC/MS
  7. washeluting with acetonitrile/water (containing 1% acetic acid)
  8. additionThe fractions containing the expected product
  9. customevaporated
  10. dissolutionThe residue was dissolved in aqueous sodium hydrogen carbonate
  11. customThe organic phase was separated
  12. dry with materialdried over magnesium sulphate
  13. customevaporated
  14. customThe residue was triturated under diethyl ether
  15. filtrationfiltered
  16. washwashed with ether
  17. dry with materialdried under vacuum over P2O5

出典と根拠

ORDレコード
ord-800dc2e9b77942bd8519550cc974aac1
出典データセット
uspto-grants-2007_09
特許番号
US07268230B2

反応ノート

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