HCID 59624586, compound → HCID 178511618, compound

HRID 1943448Notes

Reaction equation

HRID 1943448 reaction equation
C([O:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([C:18]2[N:22]3[N:23]=[C:24](Cl)[CH:25]=[C:26]([NH:27][CH:28]4[CH2:30][CH2:29]4)[C:21]3=[N:20][CH:19]=2)=[O:17])[CH:10]=1)C1C=CC=CC=1.[C@H:32]1([NH2:39])[CH2:37][CH2:36][C@H:35]([NH2:38])[CH2:34][CH2:33]1>CO>[NH2:38][C@H:35]1[CH2:36][CH2:37][C@H:32]([NH:39][C:24]2[CH:25]=[C:26]([NH:27][CH:28]3[CH2:29][CH2:30]3)[C:21]3[N:22]([C:18]([C:16]([NH:15][C:11]4[CH:10]=[C:9]([OH:8])[N:14]=[CH:13][N:12]=4)=[O:17])=[CH:19][N:20]=3)[N:23]=2)[CH2:33][CH2:34]1

Participants

4

Reactant 2

HCID 59624586HCID 59624586, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178511618HCID 178511618, compoundYield 19.12%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of N-(6-(benzyloxy)pyrimidin-4-yl)-6-chloro-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carboxamide (70 mg, 0.161 mmol, 15C) and (trans)-cyclohexane-1,4-diamine (367 mg, 3.21 mmol) was heated at 160° C. for 2 hrs. The reaction mixture was diluted with methanol and purified by preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 10% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA)) to isolate 6-((trans)-4-aminocyclohexylamino)-8-(cyclopropylamino)-N-(6-hydroxypyrimidin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (13 mg, 19.12% yield) as a white solid. LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA) Rt=1.280 minutes. [M+H]=424.15. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.35-12.78 (1H, m), 11.67 (1H, s), 8.29 (1H, s), 7.96 (1H, s), 7.69-7.94 (2H, m), 7.63 (1H, d, J=1.76 Hz), 7.05 (2H, s), 5.96 (1H, s), 3.62-3.85 (1H, m), 2.93-3.17 (1H, m), 2.05-2.24 (2H,

Workup

  1. custompurified by preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 10% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA))

Sources & evidence

ORD record
ord-5efb8cb4623041b9a053041b08b523fa
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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