Diethylamine → HCID 58770838、化合物

HRID 657263ノート

反応式

HRID 657263 の反応式
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[CH:21][CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.CCN(CC)CC.C(Cl)(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.Cl.[N+](C1C=CC(OC(=O)[NH:71][C:72]2[CH:77]=[CH:76][C:75]([N:78]3[CH2:83][CH2:82][O:81][CH2:80][CH2:79]3)=[CH:74][CH:73]=2)=CC=1)([O-])=O.C(NCC)C>C(Cl)Cl>[N:78]1([C:75]2[CH:74]=[CH:73][C:72]([NH:71][C:6]([N:8]3[CH2:13][CH2:12][CH:11]([C:14]4[C:23]5[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][N:28]6[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]6)=[CH:21][CH:22]=5)[N:17]=[CH:16][N:15]=4)[CH2:10][CH2:9]3)=[O:7])=[CH:77][CH:76]=2)[CH2:79][CH2:80][O:81][CH2:82][CH2:83]1

参加物

7

反応物 5

HCID 8021DiethylamineHCID 8471TriethylamineHCID 343679-Fluorenylmethyl chloroformateHCID 68691981HCID 68691981、化合物HCID 68947764(4-Morpholin-4-yl-phenyl)-carbamic acid 4-nitrophenyl ester hydrochloride

生成物 1

HCID 58770838HCID 58770838、化合物収率 10%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

4-[7-(3-piperazin-1-yl-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (0.05 mmol), prepared as described in Example 118, was dissolved in anhydrous DCM (1 mL) and treated with Et3N (0.05 mmol) followed by FMOC-Cl (0.1 mmol) and the mixture was stirred at rt overnight and then washed with water thrice, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. To this was added 3M HCl/MeOH (1 mL) and the mixture was stirred at rt for 2 h and then concentrated in vacuo and the residue was dissolved in a 1:1 mixture of DCM:MeOH, neutralized with excess Et3N and treated with (4-morpholin-4-yl-phenyl)-carbamic acid 4-nitrophenyl ester hydrochloride (0.06 mmol), as prepared by the method outlined in Example 66a. The mixture was stirred at rt overnight and then concentrated in vacuo and partitioned between water and DCM. DCM layer was drawn off, washed with water thrice, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1) to obtain the pure product. This was dissolved in anhydrous DCM (1 mL) and diethylamine (0.25 mL) was added and the mixture was stirred at rt overnight. It was then concentrated in vacuo and purified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1) to obtain 2.8 mg (10%) of the title compound. 1H-NMR (300 MHz, CDCl3): 9.13 (s, 1H), 8.05 (d, 1H), 7.35-7.23 (m, 4H), 6.88 (d, 2H), 6.35 (s, 1H), 4.32-4.14 (m, 4H), 3.90-3.80 (m, 4H), 3.75-3.60 (m, 1H), 3.20-2.91 (m, 10H), 2.75-2.55 (m, 6H), 2.18-1.85 (m, 7H). LC/MS (ESI): 560.0 (MH)+.

後処理

  1. washwashed with water thrice
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. additionTo this was added 3M HCl/MeOH (1 mL)
  6. stirringthe mixture was stirred at rt for 2 h
  7. concentrationconcentrated in vacuo
  8. dissolutionthe residue was dissolved in a 1:1 mixture of DCM
  9. customas prepared by the method
  10. stirringThe mixture was stirred at rt overnight
  11. concentrationconcentrated in vacuo
  12. custompartitioned between water and DCM
  13. washwashed with water thrice
  14. dry with materialdried over anhydrous MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe residue was purified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1)
  18. customto obtain the pure product
  19. stirringthe mixture was stirred at rt overnight
  20. concentrationIt was then concentrated in vacuo
  21. custompurified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1)

出典と根拠

ORDレコード
ord-fc345979f314433ebdb878e786885277
出典データセット
uspto-grants-2011_12
特許番号
US08071768B2

反応ノート

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