N'-(2-amino-7-(2-((2-((2,4-difluorophenyl)(methyl)amino)ethyl)(methyl)amino)ethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)furan-2-carbohydrazide → N1-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)-N2-(2,4-difluorophenyl)-N1,N2-dimethylethane-1,2-diamine

HRID 2239812Notes

Reaction equation

HRID 2239812 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([NH:27][NH:28][C:29]([C:31]2[O:32][CH:33]=[CH:34][CH:35]=2)=O)[C:5]2[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][N:13]([CH2:15][CH2:16][N:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[CH3:18])[CH3:14])[C:6]=2[N:7]=1>C[Si](N[Si](C)(C)C)(C)C>[NH2:1][C:2]1[N:27]2[N:28]=[C:29]([C:31]3[O:32][CH:33]=[CH:34][CH:35]=3)[N:3]=[C:4]2[C:5]2[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][N:13]([CH3:14])[CH2:15][CH2:16][N:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[CH3:18])[C:6]=2[N:7]=1

Participants

3

Reactant 1

HCID 68415842N'-(2-amino-7-(2-((2-((2,4-difluorophenyl)(methyl)amino)ethyl)(methyl)amino)ethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)furan-2-carbohydrazide

Product 1

HCID 24944547N1-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)-N2-(2,4-difluorophenyl)-N1,N2-dimethylethane-1,2-diamine

Reagents, catalysts & solvents 1

HCID 13838HexamethyldisilazaneSolvent

Conditions

Temperature
120 °C

Procedure

The title C compound, N′-(2-amino-7-(2-((2-((2,4-difluorophenyl)(methyl)amino)ethyl)-(methyl)amino)ethyl) -7H-pyrrolo[2,3-d]pyrimidin-4-yl)furan-2-carbohydrazide (crude from the previous step) (0.50 mmol) is dissolved in 2 mL of HMDS and 2 mL of BSA. The mixture is heated at 120° C. overnight, then cooled down to RT and the solvent removed in vacuo. The residue is dissolved in a mixture of DCM (2 mL) and 6N aqueous HCl (2 mL), and stirred at RT for 1 h. The pH value is adjusted to 12 using 1M aqueous NaOH. The organic phase is separated and the aqueous phase is extracted with additional DCM. The combined organic phase is dried over anhydrous Na2SO4, filtered and evaporated. The residue is purified by flash chromatography to obtain N1-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)-N2-(2,4-difluorophenyl)-N1,N2-dimethylethane-1,2-diamine: LC/MS (M+1=467). 1H NMR (DMSO-d6) δ 2.22 (s, 3H), 2.42-2.49 (m, 2H), 2.65 (s, 3H), 2.72 (t, 2H, J=6.37 Hz), 3.01 (t, 2H, J=6.81 Hz), 4.16 (t, 2H, J=6.37 Hz), 6.57 (d, 1H, J=3.42 Hz), 6.70 (dd, 1H, J=3.39 Hz and 1.78 Hz), 6.75-6.90 (m, 2H), 7.01-7.16 (m, 2H), 7.18 (dd, 1H, J=3.39 Hz and 0.81 Hz), 7.47 (s, 2H), 7.99 (dd, 1H, J=1.73 Hz and 0.81 Hz).

Workup

  1. temperaturecooled down to RT
  2. customthe solvent removed in vacuo
  3. dissolutionThe residue is dissolved in a mixture of DCM (2 mL) and 6N aqueous HCl (2 mL)
  4. customThe organic phase is separated
  5. extractionthe aqueous phase is extracted with additional DCM
  6. dry with materialThe combined organic phase is dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue is purified by flash chromatography

Sources & evidence

ORD record
ord-3a7a14b170964531a00c7e25bc2cfb5d
Source dataset
uspto-grants-2010_05
Patent number
US07723343B2

Reaction notes

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