2-Fluoro-N-methoxy-N-methylnicotinamide → (S)-tert-butyl 4-(6-(2-fluoronicotinoyl)pyrazin-2-yl)-2-isobutylpiperazine-1-carboxylate

HRID 1046565Notes

Reaction equation

I[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@@H:10]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:9]2)[CH:5]=[N:4][CH:3]=1.[F:25][C:26]1[C:31]([C:32](N(OC)C)=[O:33])=[CH:30][CH:29]=[CH:28][N:27]=1>C1COCC1>[F:25][C:26]1[N:27]=[CH:28][CH:29]=[CH:30][C:31]=1[C:32]([C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@@H:10]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:9]2)[CH:5]=[N:4][CH:3]=1)=[O:33]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of (S)-tert-butyl 4-(6-iodopyrazin-2-yl)-2-isobutylpiperazine-1-carboxylate (1.05 g, 2.353 mmol) in THF (15 mL) was cooled to −78° C. and nBuli 2.5M in hexanes (988.4 μL of 2.5 M, 2.471 mmol) was added slowly. The solution was stirred for 10 mins after which a solution of 2-fluoro-N-methoxy-N-methyl-pyridine-3-carboxamide (455.1 mg, 2.471 mmol) in THF (5 mL) was added and the solution stirred for 1 hr at −78° C. The reaction was quenched with Sat NH4Cl and extracted into EtOAc (3×30 ml). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated to give an orange oil. Columned on silica gel eluting with 1:1 EtOAc/hexanes to give (S)-tert-butyl 4-(6-(2-fluoronicotinoyl)pyrazin-2-yl)-2-isobutylpiperazine-1-carboxylate as a yellow oil (0.64 g, 61%).

Workup

additionwas added
customThe reaction was quenched with Sat NH4Cl
extractionextracted into EtOAc (3×30 ml)
washThe combined organic extracts were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated
customto give an orange oil

Sources & evidence

ORD record: ord-44615ae67633415698accd0d252da958
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569337B2

Reaction notes

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