Potassium Carbonate → 1,1-dimethylethyl (2S)-4-[(2'-fluoro-5'-{[methyl({3-[(methyloxy)carbonyl]phenyl}carbonyl)amino]methyl}-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 564526Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH2:9][N:10]([CH3:23])[C:11]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=2)[C:16]([O:18][CH3:19])=[O:17])=[O:12])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:24][C:25]([O:28][C:29]([N:31]1[CH2:36][CH2:35][N:34]([CH2:37][C:38]2[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][CH:43]=2)[CH2:33][C@@H:32]1[CH3:47])=[O:30])([CH3:27])[CH3:26].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>[F:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:9][N:10]([CH3:23])[C:11]([C:13]2[CH:22]=[CH:21][CH:20]=[C:15]([C:16]([O:18][CH3:19])=[O:17])[CH:14]=2)=[O:12])=[CH:3][C:2]=1[C:40]1[CH:41]=[CH:42][CH:43]=[C:38]([CH2:37][N:34]2[CH2:35][CH2:36][N:31]([C:29]([O:28][C:25]([CH3:27])([CH3:26])[CH3:24])=[O:30])[C@@H:32]([CH3:47])[CH2:33]2)[CH:39]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To a solution of methyl 3-{[[(3-bromo-4-fluorophenyl)methyl](methyl)amino]carbonyl}benzoate (0.20 g, 0.526 mmol) in p-dioxane/H2O (4.5/1.5 mL) was added {3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]-phenyl}boronic acid (0.264 g, 0.789 mmol), Pd(PPh3)4 (0.030 g, 0.026 mmol), and K2CO3 (0.29 mL, 2.1 mmol). The mixture was heated with z microwave at 130° C. for 15 min. The mixture was then filtered, and the filtrate concentrated and purified by CombiFlash chromatograph to afford the title compound 0.215 g (69%). LC-MS m/z 590 (M+H)+.

Workup

filtrationThe mixture was then filtered
concentrationthe filtrate concentrated
custompurified by CombiFlash chromatograph

Sources & evidence

ORD record: ord-265e841121e84128abfc03534b684750
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067408B2

Reaction notes

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