N,N-Dimethyl-1,3-propanediamine → 4-(2-(Tetrahydro-2H-pyran-4-yloxy)-6-(trifluoromethyl)pyridin-3-ylamino)-N-(3-(dimethylamino)propyl)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide

HRID 450567ノート

反応式

HRID 450567 の反応式
[O:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[C:13]([NH:14][C:15]3[C:16]4[C:23]([CH3:24])=[C:22]([C:25](OC)=[O:26])[S:21][C:17]=4[N:18]=[CH:19][N:20]=3)=[CH:12][CH:11]=[C:10]([C:29]([F:32])([F:31])[F:30])[N:9]=2)[CH2:3][CH2:2]1.[OH-].[Na+].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:68][N:69]([CH3:74])[CH2:70][CH2:71][CH2:72][NH2:73]>CCO.C1COCC1.C(Cl)Cl.OS([O-])(=O)=O.[K+]>[O:1]1[CH2:2][CH2:3][CH:4]([O:7][C:8]2[C:13]([NH:14][C:15]3[C:16]4[C:23]([CH3:24])=[C:22]([C:25]([NH:73][CH2:72][CH2:71][CH2:70][N:69]([CH3:74])[CH3:68])=[O:26])[S:21][C:17]=4[N:18]=[CH:19][N:20]=3)=[CH:12][CH:11]=[C:10]([C:29]([F:31])([F:32])[F:30])[N:9]=2)[CH2:5][CH2:6]1

参加物

9

反応物 5

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 46182174methyl 4-(2-(tetrahydro-2H-pyran-4-yloxy)-6-(trifluoromethyl)-pyridin-3-ylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate

生成物 1

HCID 461821754-(2-(Tetrahydro-2H-pyran-4-yloxy)-6-(trifluoromethyl)pyridin-3-ylamino)-N-(3-(dimethylamino)propyl)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide収率 8%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 516920Potassium bisulfate溶媒HCID 21873804Tetrahydrofuran ethanol溶媒

実験手順

To a suspension of methyl 4-(2-(tetrahydro-2H-pyran-4-yloxy)-6-(trifluoromethyl)-pyridin-3-ylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (0.139 g, 0.29 mmol) in EtOH/THF (5 mL; 3:2) was added aqueous sodium hydroxide (2 M, 0.625 mL, 1.25 mmol) and the reaction mixture stirred at ambient temperature for 24 hours. The mixture was diluted with DCM and 10% aqueous KHSO4 and the mixture separated. The organic phase was washed with brine, dried (MgSO4) and the solvent removed in vacuo. The residue was diluted with DMF (2.0 mL) and cooled in ice-water. Hünig's base (44 L, 0.25 mmol) and HATU (0.105 g, 0.28 mmol) were added and the mixture was stirred at this temperature for 20 minutes when 3-(dimethylamino)-propylamine (0.136 mL, 1.24 mmol) was added. The coolant was removed and the reaction stirred at ambient temperature for 18 hours. The mixture was diluted with EtOAc, washed with water and with brine (×2). The organic phase was dried (MgSO4), filtered and the solvent removed in vacuo. The residue was purified by flash column chromatography (100% iso-hexane→100% DCM→250:10:1 DCM/MeOH/NH4OH) followed by trituration of the major component with diethyl ether to afford the title compound as off-white solid (0.01 g, 8%).

後処理

  1. customthe mixture separated
  2. washThe organic phase was washed with brine
  3. dry with materialdried (MgSO4)
  4. customthe solvent removed in vacuo
  5. additionThe residue was diluted with DMF (2.0 mL)
  6. temperaturecooled in ice-water
  7. additionwas added
  8. customThe coolant was removed
  9. stirringthe reaction stirred at ambient temperature for 18 hours
  10. additionThe mixture was diluted with EtOAc
  11. washwashed with water and with brine (×2)
  12. dry with materialThe organic phase was dried (MgSO4)
  13. filtrationfiltered
  14. customthe solvent removed in vacuo
  15. customThe residue was purified by flash column chromatography (100% iso-hexane→100% DCM→250:10:1 DCM/MeOH/NH4OH)

出典と根拠

ORDレコード
ord-9039e4f720cc491fb84176ec402be75d
出典データセット
uspto-grants-2013_07
特許番号
US08486953B2

反応ノート

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