Water → 6-(3-(2-(diethylamino)ethoxy)phenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1755422Notes

Reaction equation

HRID 1755422 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:27]=[CH:28][N:29]=3)[N:17]=[C:18]([C:20]3[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.C([O-])([O-])=O.[K+].[K+].CS(O[CH2:41][CH2:42][N:43]([CH2:46][CH3:47])[CH2:44][CH3:45])(=O)=O.O>CN(C=O)C>[CH2:42]([N:43]([CH2:46][CH3:47])[CH2:44][CH2:45][O:26][C:22]1[CH:21]=[C:20]([C:18]2[CH:19]=[C:14]([NH:13][C:11]3[CH:10]=[CH:9][CH:8]=[C:7]([N:3]4[CH2:4][CH2:5][CH2:6][CH:2]4[CH3:1])[N:12]=3)[C:15]3[N:16]([CH:27]=[CH:28][N:29]=3)[N:17]=2)[CH:25]=[CH:24][CH:23]=1)[CH3:41]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 71526619HCID 71526619, compoundHCID 866827512-(Diethylamino)ethyl methanesulfonate

Product 1

HCID 715267016-(3-(2-(diethylamino)ethoxy)phenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amineYield 37.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenol (40 mg, 0.1 mmol) and K2CO3 (28 mg, 0.2 mmol) in DMF (5 mL) was added 2-(diethylamino)ethyl methanesulfonate (30 mg, 0.15 mmol). The mixture was heated at 50° C. for 15 h. After cooling, the mixture was poured into water and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried over MgSO4, filtrated and concentrated. The residue was purified by chromatography (silica, EtOAc) to give 6-(3-(2-(diethylamino)ethoxy)phenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (18 mg, 37%). 1H NMR (300 MHz, CDCl3): δ 8.64 (s, 1H), 8.04 (s, 1H), 7.93 (s, 1H), 7.59-7.53 (m, 3H), 7.45-7.36 (m, 2H), 7.28 (s, 1H), 7.04 (d, 1H, J=8.4 Hz), 6.23 (d, 1H, J=8.1 Hz), 6.04 (d, 1H, J=8.4 Hz), 4.29-4.15 (m, 3H), 3.68 (brs, 1H), 3.52-3.49 (m, 1H), 2.97-2.93 (m, 2H), 2.72-2.65 (m, 4 h), 2.15-2.04 (m, 3H), 1.77 (brs, 3H), 1.26 (d, 3H, J=6.3 Hz), 1.11 (t, 6H, J=7.1 Hz). LC/MS: 486 [M+H]+, tR=1.48 min. HPLC: 95.50% at 214 nm, 96.62% at 254 nm, tR=5.45 min.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltrated
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (silica, EtOAc)

Sources & evidence

ORD record
ord-04dad333999e456bbfcdf7a606cca5e7
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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