Potassium Carbonate → 1,1-Dimethylethyl 4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-1-piperazinecarboxylate

HRID 564510Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH2:9][NH2:10])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:11][C:12]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])[CH3:13].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:10][CH2:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([CH2:24][N:21]3[CH2:22][CH2:23][N:18]([C:16]([O:15][C:12]([CH3:14])([CH3:13])[CH3:11])=[O:17])[CH2:19][CH2:20]3)[CH:26]=2)[CH:3]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To two vials which each contained a solution of [(3-bromo-4-fluorophenyl)methyl]amine hydrochloric salt (0.601 g, 2.5 mmol) in p-dioxane/H2O (15/5 mL) was added {3-[(4-{[(1,1-dimethylethyl)oxy]carbonyl}-1-piperazinyl)methyl]phenyl}boronic acid (1.2 g, 3.75 mmol), Pd(PPh3)4 (145 mg, 0.125 mmol), and K2CO3 (1.38 g, 10 mmol). The mixture was heated with a microwave at 150° C. for 15 min. The organic layer of both vials was separated, combined, concentrated and purified by CombiFlash chromatograph to afford the title compound 1.98 g (99%). LC-MS m/z 400 (M+H)+.

Workup

customThe organic layer of both vials was separated
concentrationconcentrated
custompurified by CombiFlash chromatograph

Sources & evidence

ORD record: ord-51de4f207dd64f7380c6e6be90b3a54d
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067408B2

Reaction notes

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