Trifluoroacetic acid → HCID 178511628, compound

HRID 1943399Notes

Reaction equation

HRID 1943399 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([C:27](=[O:32])[NH:28][CH:29]3[CH2:31][CH2:30]3)=[CH:23][CH: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:33]1([NH2:40])[CH2:38][CH2:37][C@H:36]([NH2:39])[CH2:35][CH2:34]1.C(O)(C(F)(F)F)=O>>[NH2:39][C@H:36]1[CH2:37][CH2:38][C@H:33]([NH:40][C:2]2[CH:3]=[C:4]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27](=[O:32])[NH:28][CH:29]4[CH2:31][CH2:30]4)=[CH:23][CH: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)[CH2:34][CH2:35]1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 596246816-Chloro-8-[[4-[(cyclopropylamino)carbonyl]phenyl]amino]-N-4-pyridinylimidazo[1,2-b]pyridazine-3-carboxamideHCID 178511674HCID 178511674, compound

Product 1

HCID 178511628HCID 178511628, compoundYield 26.4%

Conditions

Temperature
160 °C

Procedure

To a 1 dram vial was added 6-chloro-8-(4-(cyclopropylcarbamoyl)phenylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (39 mg, 0.087 mmol) and (trans)-cyclohexane-1,4-diamine (99 mg, 0.871 mmol). The reaction solution was heated neat at 160° C. for 1 hour. The solution was cooled and purified by preparative HPLC to yield 6-((trans-4-aminocyclohexyl)amino)-8-((4-(cyclopropylcarbamoyl)phenyl)amino)-N-4-pyridinylimidazo[1,2-b]pyridazine-3-carboxamide (11.90 mg, 0.023 mmol, 26.0% yield) as a TFA salt. 1H NMR (500 MHz, CD3OD) δ ppm 8.73-8.76 (2H, m), 8.28-8.32 (2H, m), 8.19 (1H, s), 7.86-7.90 (2H, m), 7.41-7.45 (2H, m), 6.48-6.50 (1H, m), 3.78-3.85 (1H, m), 3.14-3.21 (1H, m), 2.83-2.88 (1H, m), 2.32-2.38 (2H, m), 2.12-2.18 (3H, m), 1.55-1.64 (3H, m), 1.42-1.51 (3H, m), 0.78-0.84 (2H, m), 0.62-0.69 (2H, m) LC/MS, m/z 526.17 (M+1). HPLC Rt, 2.21 min. 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.

Workup

  1. temperatureThe solution was cooled
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-523aed5bf0464c3598d81d1964bda73e
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

Loading…