Diisopropylethylamine → 2,2-dimethyl-N-[2-methyl-5-[6-(3-methylaminopyrrolidin-1-yl)imidazo[2,1-f]pyridazin-2-yl]phenyl]propanamide

HRID 539791Notes

Reaction equation

C(N(C(C)C)CC)(C)C.[CH3:10][NH:11][CH:12]1[CH2:16][CH2:15][NH:14][CH2:13]1.Cl[C:18]1[CH:23]=[CH:22][C:21]2=[N:24][C:25]([C:27]3[CH:28]=[CH:29][C:30]([CH3:40])=[C:31]([NH:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36])[CH:32]=3)=[CH:26][N:20]2[N:19]=1>C(O)CCC>[CH3:36][C:35]([CH3:38])([CH3:37])[C:34]([NH:33][C:31]1[CH:32]=[C:27]([C:25]2[N:24]=[C:21]3[N:20]([CH:26]=2)[N:19]=[C:18]([N:14]2[CH2:15][CH2:16][CH:12]([NH:11][CH3:10])[CH2:13]2)[CH:23]=[CH:22]3)[CH:28]=[CH:29][C:30]=1[CH3:40])=[O:39]

Participants

Conditions

Temperature: 180 °C

Procedure

An small microwave vial is charged butanol (0.183 mL), diisopropylethylamine (0.122 mL, 0.7 mmol), N-methylpyrrolidin-3-amine (0.050 g, 0.5 mmol), and N-[5-(6-chloroimidazo[2,1-f]pyridazin-2-yl)-2-methyl-phenyl]-2,2-dimethyl-propanamide (0.0397 g, 0.1 mmol). The vial is sealed and heated at 180° C. for 30 min in microwave. The mixture is concentrated, taken up in DMSO and purified on reverse phase preparative HPLC with gradient (15% B:85% A to 100% B, where solvent A=95% water, 5% acetonitrile and 0.1% TFA; solvent B=90% acetonitrile, 10% water and 0.1% TFA) to give the title compound (0.006 g, 15% yield). LCMS m/z=407.6 [M+H]+, tR=1.32 min. (compound same as Example 360)

Workup

customThe vial is sealed
concentrationThe mixture is concentrated
custompurified on reverse phase preparative HPLC with gradient (15% B:85% A to 100% B, where solvent A=95% water, 5% acetonitrile and 0.1% TFA; solvent B=90% acetonitrile, 10% water and 0.1% TFA)

Sources & evidence

ORD record: ord-cebd0aa441eb4fa49471471706e27c6c
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871767B2

Reaction notes

Loading…