Water → HCID 10125856, compound

HRID 729350Notes

Reaction equation

HRID 729350 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][C:10]2[N:11]([N:13]=[CH:14][C:15]=2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]3[CH2:25][CH2:24]3)[N:17]=2)[N:12]=1)(=O)=O.CCN(C(C)C)C(C)C.[CH:37]1([NH2:42])[CH2:41][CH2:40][CH2:39][CH2:38]1.O>CN(C=O)C>[CH:37]1([NH:42][C:7]2[CH:8]=[CH:9][C:10]3[N:11]([N:13]=[CH:14][C:15]=3[C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]4[CH2:25][CH2:24]4)[N:17]=3)[N:12]=2)[CH2:41][CH2:40][CH2:39][CH2:38]1

Participants

6

Reactant 4

HCID 962WaterHCID 2906Cyclopentylamine2×HCID 81531Diisopropylethylamine2×HCID 10172978HCID 10172978, compound

Product 1

HCID 10125856HCID 10125856, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3-[2-(cyclopropylamino)-pyrimidinyl]pyrazolo[1,5-b]pyridazin-6-yl trifluoromethanesulfonate (107 mg, 0.268 mmol) in DMF (2 mL) was added DIEA (0.093 mL, 0.536 mmol) and cyclopentylamine (0.026 mL, 0.268 mmol). The reaction mixture was heated at an oil bath temperature of 50° C. for about 1 hour at which point N-phenyltrifluoromethylsulfonimide (95 mg, 0.268 mmol) was added followed by an additional portion (equivalent) of cyclopentylamine and DIEA. This was repeated two more times. The mixture was cooled to RT and water (20 mL) was added. The aqueous layer was washed with EtOAc (3×50 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo and purified by silica-gel column chromatography (gradient, 0-10% MeOH in CH2Cl2). The residue was suspended in EtOAc and triturated with hexanes to give the title compound as a yellow solid (26 mg, 29%). 1H-NMR (300 MHz, CDCl3) δ 8.71 (d, 1H, J=9.5 Hz), 8.17 (s, 2H), 6.89 (d, 1H, J=5.7 Hz), 6.55 (d, 1H, J=9.3 Hz), 5.92 (bs, 1H), 4.43 (m, 1H), 4.30 (m, 1H), 2.84 (m, 1H), 2.16 (m, 2H), 1.71 (m, 4H), 1.50 (m, 2H), 0.87 (m, 2H), 0.66 (m, 2H); MS (APCI) (M+H)+ 336.

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to RT
  3. washThe aqueous layer was washed with EtOAc (3×50 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by silica-gel column chromatography (gradient, 0-10% MeOH in CH2Cl2)
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-56a0789f0e9f472cace2bc2007a9a695
Source dataset
uspto-grants-2009_09
Patent number
US07582630B2

Reaction notes

Loading…