Water → Tert-butyl-4-(2-(3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenoxy)ethyl)piperazine-1-carboxylate

HRID 1755428Notes

Reaction equation

HRID 1755428 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][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][CH2:44]1)(=O)=O.O>CN(C=O)C>[C:52]([O:51][C:49]([N:46]1[CH2:47][CH2:48][N:43]([CH2:42][CH2:41][O:26][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([C:18]3[CH:19]=[C:14]([NH:13][C:11]4[CH:10]=[CH:9][CH:8]=[C:7]([N:3]5[CH2:4][CH2:5][CH2:6][CH:2]5[CH3:1])[N:12]=4)[C:15]4[N:16]([CH:27]=[CH:28][N:29]=4)[N:17]=3)[CH:21]=2)[CH2:44][CH2:45]1)=[O:50])([CH3:55])([CH3:54])[CH3:53]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 22989493Tert-butyl 4-(2-(methylsulfonyloxy)ethyl)piperazine-1-carboxylateHCID 71526619HCID 71526619, compound

Product 1

HCID 86682754Tert-butyl-4-(2-(3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenoxy)ethyl)piperazine-1-carboxylateYield 33%

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 (50 mg, 0.129 mmol) and K2CO3 (36 mg, 0.258 mmol) in DMF (5 mL) was added tert-butyl 4-(2-(methylsulfonyloxy)ethyl)piperazine-1-carboxylate (48 mg, 0.155 mmol). The mixture was heated at 50° C. for 16 h. After cooling, the mixture was poured into water and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine and dried over MgSO4. After filtration and concentration, the residue was washed by petroleum ether to give tert-butyl-4-(2-(3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenoxy)ethyl)piperazine-1-carboxylate (25 mg, 33%) as crude oil. LC-MS: 599.4 [M+H]+, tR=1.53 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. filtrationAfter filtration and concentration
  6. washthe residue was washed by petroleum ether

Sources & evidence

ORD record
ord-30e2eddadd6549d29b2d859fd8eb54ea
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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