6-chloro-N-(4-ethoxyphenyl)-7-methylimidazo[1,2-b]pyridazin-8-amine → HCID 178466724, compound

HRID 2239835Notes

Reaction equation

HRID 2239835 reaction equation
Cl[C:2]1[C:3]([CH3:21])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH3:20])=[CH:14][CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[NH2:22][C@H:23]1[CH2:28][CH2:27][C@@H:26]([NH2:29])[CH2:25][CH2:24]1>CO>[NH2:22][C@@H:23]1[CH2:28][CH2:27][C@H:26]([NH:29][C:2]2[C:3]([CH3:21])=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH3:20])=[CH:14][CH:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=2)[CH2:25][CH2:24]1

Participants

4

Reactant 2

HCID 866117156-chloro-N-(4-ethoxyphenyl)-7-methylimidazo[1,2-b]pyridazin-8-amineHCID 178511673HCID 178511673, compound

Product 1

HCID 178466724HCID 178466724, compoundYield 11.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
165 °C

Procedure

To 6-chloro-N-(4-ethoxyphenyl)-7-methylimidazo[1,2-b]pyridazin-8-amine (40 mg, 0.14 mmol) from Example III(1), step 1d was added cis-1,4-diaminocyclohexane (250 mg, 2.19 mmol). The mixture was allowed to heat at 165° C. for 48 hrs. The reaction mixture then cooled, diluted with methanol and purified by preparative HPLC. The eluent was then concentrated in vacuo, diluted with methanol (2 mL), purified and neutralized by passing through a 500 mg SCX (Cation exchange column). The eluent was concentrated to give 6.0 mg (11.3%) of the titled compound. 1H NMR (500 MHz, MeOH) δ ppm 7.65 (1H, s), 7.25 (1H, s), 6.85 (4 H, m), 3.95 (2H, d, J=7.2 Hz), 3.95 (1H, m), 3.05 (1H, m), 1.95 (2H, m), 1.85 (3H, s), 1.80 (4H, m), 1.65 (2H, m), 1.35 (3H, t, J=7.2 Hz). LC/MS m/e 381 (M+1). HPLC, 1.91 min. Waters Sunfire C18 4.6×50.0%-100% B. B: 90% MeOH, 10% H2O, 0.1% TFA. A: 10% MeOH, 90% H2O, 0.1% TFA, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

Workup

  1. temperatureThe reaction mixture then cooled
  2. custompurified by preparative HPLC
  3. concentrationThe eluent was then concentrated in vacuo
  4. additiondiluted with methanol (2 mL)
  5. custompurified
  6. concentrationThe eluent was concentrated

Sources & evidence

ORD record
ord-2786996a9fd6445281223e2956c8180f
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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