Diisopropylethylamine → tert-Butyl 5-((1H-pyrazole-4-carboxamido)methyl)-4,6-dimethylpyridin-2-ylcarbamate

HRID 928445Notes

Reaction equation

[NH:1]1[CH:5]=[C:4]([C:6]([O:8]CC)=O)[CH:3]=[N:2]1.[CH3:11]CN(C(C)C)C(C)C.[NH2:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[N:26][C:27]=1[CH3:28].CCCP(=O)=O>CN(C=O)C.C(OCC)(=O)C.O>[NH:2]1[CH:3]=[C:4]([C:6]([NH:20][CH2:21][C:22]2[C:23]([CH3:11])=[CH:24][C:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[N:26][C:27]=2[CH3:28])=[O:8])[CH:5]=[N:1]1

Participants

Conditions

Temperature: 0 °C

Procedure

The starting material ethyl pyrazole-4-carboxylate was saponified in analogy to Example 157, Step a), To a solution of the free acid (1 g, 5.86 mmol) in DMF (40 ml) were added DIPEA (4.10 ml, 23.46 mmol) and tert-butyl (5-(aminomethyl)-6-methylpyridin-2-yl)carbamate (1.531 g, 6.45 mmol). At 0° C., propylphosphonic anhydride (50% in DMF, 3.42 ml, 5.86 mmol) was added dropwise. Reaction mixture was stirred for 30 min at 0° C., then diluted with ethyl acetate and water. Phases were separated and organic layer was washed with NaHCO3 sat. solution and brine. Organic layer was dried over sodium sulfate, filtered and evaporated to afford the crude material, which was purified by silicagel chromatography (DCM/MeOH from 100/0 to 9/1 in 30 min) to afford the title compound. HPLC (Method G) Rt=1.209 min, MS (Method V) [M+H]+=332.3.

Workup

customReaction mixture
customPhases were separated
washorganic layer was washed with NaHCO3 sat. solution and brine
dry with materialOrganic layer was dried over sodium sulfate
filtrationfiltered
customevaporated
customto afford the crude material, which
customwas purified by silicagel chromatography (DCM/MeOH from 100/0 to 9/1 in 30 min)

Sources & evidence

ORD record: ord-489ca6eaf2244d638c85f9d2a1f6c8c9
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290485B2

Reaction notes

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