HCID 59624858, compound → HCID 178426347, compound

HRID 1943438Notes

Reaction equation

HRID 1943438 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N:20](CC2C=CC(OC)=CC=2)[C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][N:22]=2)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[C@H:37]1([NH2:44])[CH2:42][CH2:41][C@H:40]([NH2:43])[CH2:39][CH2:38]1>C(Cl)Cl>[NH2:43][C@H:40]1[CH2:41][CH2:42][C@H:37]([NH:44][C:2]2[CH:3]=[C:4]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][N:22]=3)[C:5]3[N:6]([C:8]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=4)=[O:12])=[CH:9][N:10]=3)[N:7]=2)[CH2:38][CH2:39]1

Participants

4

Reactant 2

HCID 59624858HCID 59624858, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178426347HCID 178426347, compoundYield 48.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
160 °C

Procedure

To a 2 dram vial was added 6-chloro-8-((4-methoxybenzyl)(5-methylpyridin-2-yl)amino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (32 mg, 0.064 mmol) and (trans)-cyclohexane-1,4-diamine (146 mg, 1.280 mmol). The reaction mixture was heated neat at 160° C. for 1 hour. The solution was diluted with DCM and washed with water. The organic layer was concentrated to dryness and then dissolved in neat TFA and heated to 80° C. for 2 hours. The solution was concentrated in vacuo and the residue was purified via preparative HPLC to give 6-((trans-4-aminocyclohexyl)amino)-8-((5-methyl-2-pyridinyl)amino)-N-4-pyridinylimidazo[1,2-b]pyridazine-3-carboxamide (14.2 mg, 0.031 mmol, 48.5% yield). HPLC Rt=2.19 minutes (Waters Sunfire C18 column 4.6×50 mm):0%-100% B. Solvent B: 90% MeOH, 10% H2O, 0.1% TFA). Solvent A: 10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min) [M+H]=458.

Workup

  1. washwashed with water
  2. concentrationThe organic layer was concentrated to dryness
  3. dissolutiondissolved in neat TFA
  4. temperatureheated to 80° C. for 2 hours
  5. concentrationThe solution was concentrated in vacuo
  6. customthe residue was purified via preparative HPLC

Sources & evidence

ORD record
ord-d99ec11c70f743c9b6af506d745e6f24
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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