Thionyl Chloride → N-(3-ethyl-1-((6-methoxypyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79298

Reaction equation

[N:1]1[CH:2]=[C:3]([C:10]([OH:12])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.S(Cl)(Cl)=O.ClCCCl.C1COCC1.[CH2:26]([C:28]1[C:36]2[C:35]([NH2:37])=[CH:34][CH:33]=[CH:32][C:31]=2[N:30]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([O:45][CH3:46])[N:40]=2)[N:29]=1)[CH3:27]>C(Cl)Cl>[CH2:26]([C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][C:35]=2[NH:37][C:10]([C:3]2[N:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]3=[N:1][CH:2]=2)=[O:12])[N:30]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([O:45][CH3:46])[N:40]=2)[N:29]=1)[CH3:27]

Participants

Conditions

Temperature: 70 °C

Procedure

To imidazo[1,2-a]pyridine-3-carboxylic acid (194 mg, 1.20 mmol) in DCM (5 mL) was added thionyl chloride (2 mL). The reaction mixture was stirred for 2 hours and concentrated to give crude acylchloride HCl salt, to which DCE/THF (2 mL/2 mL) and 3-ethyl-1-((6-methoxypyridin-2-yl)methyl)-1H-indazol-4-amine (211 mg, 0.747 mmol) was added. The reaction mixture was heated to 70° C. and stirred for 1 hour. The reaction mixture was diluted with DCM (20 mL) and washed with saturated NaHCO3 aqueous solution. The organic solution was dried over Na2SO4, filtered and concentrated. Silica gel chromatography (DCM/MeOH 10:1) provided the desired product (226 mg). MS (ES+APCI) m/z=427 (M+H).

Workup

concentrationconcentrated
customto give crude acylchloride HCl salt
stirringstirred for 1 hour
washwashed with saturated NaHCO3 aqueous solution
dry with materialThe organic solution was dried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-c00b4facc8a94ea88374eda9c0943ec1
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841455B2

Linked notes

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