Water → 6-Amino-5-chloro-N-{[1-(cyclohexylmethyl)-4-piperidinyl]methyl}-2-(methyloxy)-3-pyridinecarboxamide

HRID 489800Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([NH:12][CH2:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:11])=[CH:4][C:3]=1[Cl:20].Br[CH2:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.C(N(CC)CC)C.O>CN(C)C=O>[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([NH:12][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([CH2:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[CH2:16][CH2:15]2)=[O:11])=[CH:4][C:3]=1[Cl:20]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 6-amino-5-chloro-2-(methyloxy)-N-(4-piperidinylmethyl)-3-pyridinecarboxamide (step 1, 150 mg, 0.50 mmol), (bromomethyl)cyclohexane (107 mg, 0.60 mmol), and triethylamine (140 μl, 1.00 mmol) in N,N-dimethylformamide (5 ml) was stirred at 90° C. for 10 h. After cooling to room temperature, the mixture was poured into water (50 ml) and the aqueous layer was extracted with ethyl acetate/toluene (2:1, 80 ml×2). The combined organic layer was washed with brine (100 ml), dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting with 25% ammonia/methanol/dichloromethane (0.1:1:20) to give 130 mg (65%) of the title compound as a yellow amorphous solid.

Workup

temperatureAfter cooling to room temperature
extractionthe aqueous layer was extracted with ethyl acetate/toluene (2:1, 80 ml×2)
washThe combined organic layer was washed with brine (100 ml)
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customThe residue was chromatographed on a column of silica gel eluting with 25% ammonia/methanol/dichloromethane (0.1:1:20)

Sources & evidence

ORD record: ord-1f779115765249259090aa9523048673
Source dataset: uspto-grants-2005_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06979690B2

Reaction notes

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