N,N-Dimethyl-1,3-propanediamine → HCID 46182213, compound

HRID 450569Notes

Reaction equation

HRID 450569 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:11]=[C:10]([O:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:9]([NH:19][C:20]3[C:21]4[C:28]([CH3:29])=[C:27]([C:30]([O:32]C)=O)[S:26][C:22]=4[N:23]=[CH:24][N:25]=3)=[CH:8][CH:7]=2)=[CH: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.[CH3:69][N:70]([CH3:75])[CH2:71][CH2:72][CH2:73][NH2:74]>CCO.C1COCC1.C(Cl)Cl.OS([O-])(=O)=O.[K+]>[CH3:69][N:70]([CH3:75])[CH2:71][CH2:72][CH2:73][NH:74][C:30]([C:27]1[S:26][C:22]2[N:23]=[CH:24][N:25]=[C:20]([NH:19][C:9]3[C:10]([O:12][CH:13]4[CH2:14][CH2:15][O:16][CH2:17][CH2:18]4)=[N:11][C:6]([C:3]4[CH:4]=[CH:5][O:1][CH:2]=4)=[CH:7][CH:8]=3)[C:21]=2[C:28]=1[CH3:29])=[O:32]

Participants

9

Reactant 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 46182214HCID 46182214, compound

Product 1

HCID 46182213HCID 46182213, compoundYield 11.3%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 516920Potassium bisulfateSolventHCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

To a suspension of methyl 4-(6-(furan-3-yl)-2-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-ylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (0.155 g, 0.33 mmol) in EtOH/THF (5 mL, 3:2) was added aqueous sodium hydroxide (2M, 0.714 mL, 1.43 mmol) and the reaction mixture stirred at ambient temperature for 24 hours. The mixture was diluted with DCM and 10% aqueous KHSO4 and the organic layer 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 (32 L, 0.18 mmol) and HATU (0.076 g, 0.20 mmol) were added and the mixture was stirred at this temperature for 20 minutes when 3-(dimethylamino)-propylamine (0.100 mL, 0.91 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 brine (×2). The organic phase was dried (MgSO4), filtered and the solvent was removed in vacuo. The residue was purified by SCX-2 ion exchange chromatography to afford the title compound as an off-white solid (0.02 g, 11%).

Workup

  1. customthe organic layer 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 brine (×2)
  12. dry with materialThe organic phase was dried (MgSO4)
  13. filtrationfiltered
  14. customthe solvent was removed in vacuo
  15. customThe residue was purified by SCX-2 ion exchange chromatography

Sources & evidence

ORD record
ord-dafcd3d99fa64218b6d7bcc9dfe2dad1
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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