Acetic Acid → 2-{6-[5-Fluoro-4-methoxy-2-(2,2,2-trifluoro-ethyl)-phenyl]-1H-indazol-3-yl}-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine trihydrochloride salt

HRID 2038738Notes

Reaction equation

CO[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[C:18]([F:20])[C:17]([O:21][CH3:22])=[CH:16][C:15]=3[CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:11][CH:12]=2)[N:7](C2CCCCO2)[N:6]=1)=[NH:4].C(OC([N:41]1[CH2:46][CH2:45][C:44](OCC)(OCC)[CH:43]([NH2:53])[CH2:42]1)=O)(C)(C)C.C(O)(=O)C.[ClH:58]>C(O)C>[ClH:58].[ClH:58].[ClH:58].[F:20][C:18]1[C:17]([O:21][CH3:22])=[CH:16][C:15]([CH2:23][C:24]([F:27])([F:26])[F:25])=[C:14]([C:10]2[CH:9]=[C:8]3[C:13]([C:5]([C:3]4[NH:53][C:43]5[CH2:42][NH:41][CH2:46][CH2:45][C:44]=5[N:4]=4)=[N:6][NH:7]3)=[CH:12][CH:11]=2)[CH:19]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 6-[5-fluoro-4-methoxy-2-(2,2,2-trifluoro-ethyl)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboximidic acid methyl ester (Preparation 37, 1.64 g, 3.78 mmol) in ethanol (5 mL) was added a solution of 3-amino-4,4-diethoxy-piperidine-1-carboxylic acid tert-butyl ester (US-2004/0229862, 1.15 g, 3.97 mmol) in ethanol (7.5 mL). Acetic acid (430 μL, 7.56 mmol) was added and the reaction mixture was heated at 50° C. for 18 hours and then concentrated in vacuo to give a brown oil. The oil was dissolved in ethanol (15 mL) and the resulting solution was treated with concentrated hydrochloric acid (12M, 4.75 mL, 56.7 mmol) and then heated at 80° C. for 18 hours. The solvent was removed in vacuo to yield the title compound (2.03 g) in a 97% yield.

Workup

concentrationconcentrated in vacuo
customto give a brown oil
temperatureheated at 80° C. for 18 hours
customThe solvent was removed in vacuo

Sources & evidence

ORD record: ord-7ee431f61ba140a282555e36231844e2
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575336B2

Reaction notes

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