Diisopropylethylamine → 1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-5,8-dihydro-6H-9-thia-1,3,7-triaza-fluoren-7-yl]-5-(tetrahydro-pyran-2-yloxy)-pent-2-en-1-one

HRID 1887420

反応式

HRID 1887420 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:29]3[C:28]4[CH2:27][CH2:26][NH:25][CH2:24][C:23]=4[S:22][C:21]=3[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[O:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]1[O:36][CH2:37][CH2:38][CH:39]=[CH:40][C:41](O)=[O:42].C(N(C(C)C)CC)(C)C>ClCCl.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:29]3[C:28]4[CH2:27][CH2:26][N:25]([C:41](=[O:42])[CH:40]=[CH:39][CH2:38][CH2:37][O:36][CH:31]5[CH2:32][CH2:33][CH2:34][CH2:35][O:30]5)[CH2:24][C:23]=4[S:22][C:21]=3[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 59586947[3-Chloro-4-(pyridin-2-ylmethoxy)-phenyl]-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)amineHCID 668767525-(Tetrahydro-pyran-2-yloxy)-pent-2-enoic acid

生成物 1

HCID 668777681-[4-[3-chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-5,8-dihydro-6H-9-thia-1,3,7-triaza-fluoren-7-yl]-5-(tetrahydro-pyran-2-yloxy)-pent-2-en-1-one収率 79.2%

試薬・触媒・溶媒 1

HCID 21919333Tetrahydrofurane dichloromethane溶媒

実験手順

In a 100 ml rb flask were placed [3-chloro-4-(pyridine-2-ylmethoxy)-phenyl]-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amine (2.0, 4.71 mmol), 5-(tetrahydro-pyran-2-yloxy)-pent-2-enoic acid (0.94 g, 4.71 mmol) and O-(Benzotriazol-1-yl)-N,N,N′,N′-tetrafluorobonate (1.81 g, 5.66 mmol) in anhydrous dichloromethane/THF (15 ml/15 ml) and cooled at 0° C. To this cooled suspension was slowly added diisopropylethylamine (1.83 g, 14.15 mmol) (2.5 ml) during 15 minute. Then the reaction mixture was warmed to room temperature and stirred at room temperature for 12 hours. The reaction mixture was concentrated at room temperature (no heating) to remove dichloromethane. To the residue was added water and precipitated grey-white solid was filtered and washed with water. The grey-white solid was further suspended in methyl alcohol, sonicated, filtered and dried to provide 2.26 g of grey-white solid. (80.0%). It will be carried to next step reaction without any purification. 1H-NMR (DMSO-d6) δ 8.593-8.575 (m, 1H), 8.391 (s, 1H), 8.191 (s, 1H), 7.872-7.868 (m, 1H), 7.769 (s, 1H) 7.571-7.498 (m, 2H), 7.369-7.329 (m, 1H), 7.236-7.214 (d, 1H), 6.779-6.607 (m, 2H), 5.274 (s, 2H), 4.946-4.835 (d, 2H), 4.572 (s, 1H), 3.928-3.730 (m, 2H), 3.504-3.402 (m, 2H), 3.313-3.204 (m, 4H), 1.673-1.434 (m, 8H). MS m/e 605.9 (M+H), RT=3.02 min

後処理

  1. customIn a 100 ml rb flask were placed
  2. customduring 15 minute
  3. concentrationThe reaction mixture was concentrated at room temperature (no heating)
  4. customto remove dichloromethane
  5. additionTo the residue was added water
  6. customprecipitated grey-white solid
  7. filtrationwas filtered
  8. washwashed with water
  9. customsonicated
  10. filtrationfiltered
  11. customdried

出典と根拠

ORDレコード
ord-f56a5b58e2fa4aeb897bcbde2d537c1d
出典データセット
uspto-grants-2013_08
特許番号
US08501755B2

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