Water → HCID 71526698, compound

HRID 1755419Notes

Reaction equation

HRID 1755419 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:40][CH2:41][CH2:42][N:43]1[CH2:48][CH2:47]C[CH2:45][CH2:44]1)(=O)=O.O>CN(C=O)C>[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:25]=[CH:24][CH:23]=[C:22]([O:26][CH2:45][CH2:44][N:43]4[CH2:42][CH2:41][O:40][CH2:47][CH2:48]4)[CH:21]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 446269212-Piperidin-1-ylethyl methanesulfonateHCID 71526619HCID 71526619, compound

Product 1

HCID 71526698HCID 71526698, compoundYield 40%

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-(piperidin-1-yl)ethyl methanesulfonate (25 mg, 0.12 mmol). The mixture was heated at 50° C. for 16 h. After cooling, the mixture was poured into water and extracted with EtOAc (10 mL×3). The combined organic layers were washed with brine, then dried over MgSO4. After filtration and concentration, the residue was purified by chromatography (silica, EtOAc) to give N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-(3-(2-morpholinoethoxy)phenyl)imidazo[1,2-b]pyridazin-8-amine (20 mg, 40%). 1H NMR (300 MHz, CDCl3): δ 8.65 (s, 1H), 8.06 (s, 1H), 7.93 (s, 1H), 7.59-7.54 (m, 3H), 7.45-7.40 (m, 2H), 7.04-7.02 (m, 2H), 6.22 (d, 1H, J=7.5 Hz), 6.04 (d, 1H, J=7.8 Hz), 4.25-4.20 (m, 3H), 3.79-3.76 (m, 4 h), 3.68 (brs, 1H), 3.51-3.48 (m, 1H), 2.87 (t, 2H, J=5.7 Hz), 2.64 (brs, 4 h), 2.14-2.06 (m, 3H), 1.78 (brs, 1H), 1.67-1.62 (m, 4 h), 1.50-1.48 (m, 2H), 1.25 (d, 3H, J=6.3 Hz). LC/MS: 500 [M+H]+, tR=1.13 min. HPLC: 95.85% at 214 nm, 95.41% at 254 nm, tR=5.12 min.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc (10 mL×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by chromatography (silica, EtOAc)

Sources & evidence

ORD record
ord-3dd8d13d3e4645daa5d787cb46b0e944
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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