2-Bromo-5-fluoropyridine → HCID 118022836, compound

HRID 1498871Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[Li]CCCC.[C:14]([C:17]1[CH:18]=[N:19][C:20]([N:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:30])[CH2:25][CH2:24]2)=[N:21][CH:22]=1)(=[O:16])[CH3:15]>C1COCC1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:14]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)([OH:16])[CH3:15])=[N:3][CH:4]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2-bromo-5-fluoropyridine (1.3 g, 7.50 mmol) in anhydrous THF (30 mL) was added n-BuLi (2.76 mL, 6.62 mmol) at −78° C. dropwise, and the mixture was stirred at −78° C. for 2 h, followed by the addition of benzyl 4-(5-acetylpyrimidin-2-yl)piperazine-1-carboxylate (1.5 g, 4.41 mmol). The reaction mixture was allowed to warm to RT and stirred overnight. LCMS showed the reaction was completed. The solution was quenched with aqueous NH4Cl (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (2×50 mL) and brine (50 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by Prep-HPLC to afford the title compound (0.4 g, 20%) as a white solid. MS (ES+) C23H24FN5O3 requires: 437. found: 438 [M+H]+.

Workup

temperatureto warm to RT
stirringstirred overnight
customThe solution was quenched with aqueous NH4Cl (50 mL)
extractionextracted with EtOAc (3×100 mL)
washThe combined organic layers were washed with water (2×50 mL) and brine (50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by Prep-HPLC

Sources & evidence

ORD record: ord-1ec45b3517a142eb9d5f95f43f864b52
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200002B2

Reaction notes

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