Water → HCID 71526620, compound

HRID 1755418Notes

Reaction equation

HRID 1755418 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]1[CH2:48][CH2:47][CH2:46][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][CH2:41][CH2:42][N:43]4[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]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 71526620HCID 71526620, compoundYield 40.2%

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 (8 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 gel, EtOAc) to give N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-(3-(2-(piperidin-1-yl)ethoxy)phenyl)imidazo[1,2-b]pyridazin-8-amine (20 mg, 40%). 1H NMR (300 MHz, CDCl3): δ 8.67 (s, 1H), 8.08 (s, 1H), 7.93 (s, 1H), 7.60-7.53 (m, 3H), 7.45-7.37 (m, 2H), 7.05-7.01 (m, 1H), 6.23 (d, 1H, J=7.5 Hz), 6.04 (d, 1H, J=8.4 Hz), 4.31-4.21 (m, 3H), 3.71-3.65 (m, 1H), 3.54-3.48 (m, 1H), 2.85 (t, 2H, J=6.0 Hz), 2.57 (brs, 4 h), 2.17-2.04 (m, 3H), 1.76-1.62 (m, 5H), 1.48 (brs, 2H), 1.26 (d, 3H, J=6.6 Hz). LC/MS: 498 [M+H]+, tR=1.15 min. HPLC: 99.14% at 214 nm, 99.51% at 254 nm, tR=3.97 min.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc (8 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 gel, EtOAc)

Sources & evidence

ORD record
ord-86429af23a2b46838eea8cd9bf3bbf16
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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