Ammonium Chloride → 2-Chloro-6-fluoro-N-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-benzamide hydrogen chloride salt

HRID 1822046Notes

Reaction equation

[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9]2[N:14]=[C:13]([NH2:15])[CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[Cl:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:18]=1[C:19](Cl)=[O:20].N.CO.[NH4+].[Cl-]>CO.O1CCOCC1>[ClH:16].[Cl:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:18]=1[C:19]([NH:15][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([O:8][CH:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)[N:14]=1)=[O:20]

Participants

Conditions

Temperature: 50 °C

Procedure

Combine 6-(1-methyl-piperidin-4-yloxy)-pyridin-2-ylamine (preparation 60, 200 mg, 0.96 mmol), and dioxane (15 mL), stir and heat at 50° C. Add 2-chloro-6-fluorobenzoyl chloride (214 □L, 1.1 mmol), and heat at 85° C. for an additional 3 hr. Cool the reaction to room temperature, and load onto a 5 g SCX cartridge. Wash resin with Methanol, then remove product with 2 M NH3/methanol. Concentrate in vacuo, and silica gel chromatography eluting with 5-20% 2 M NH3 in methanol/methylene dichloride. Dissolve the purified oil (286 mg, 81% isolated yield) in methanol, add NH4Cl (42 mg, 1 eq) as a solid, and sonicate the solution at room temperature for 15 min. Concentration in vacuo provides the title compound: mass spectrum (ion spray): m/z=364.1 (M+1); mp=139.6° C.

Workup

temperatureCool
customthe reaction to room temperature
concentrationConcentrate in vacuo, and silica gel chromatography
washeluting with 5-20% 2 M NH3 in methanol/methylene dichloride
dissolutionDissolve
customthe purified oil (286 mg, 81% isolated yield) in methanol
customsonicate the solution at room temperature for 15 min
concentrationConcentration in vacuo

Sources & evidence

ORD record: ord-13890d9d5dd44347a463c2252fbffdef
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608629B2

Reaction notes

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