Water → HCID 86590538, compound

HRID 1620899Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:13][C@H:14]([C:19]([NH:21][CH2:22][C:23]#[N:24])=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][N:35](C2C=CC(B(O)O)=CC=2)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:23]([CH2:22][NH:21][C:19]([C@@H:14]([NH:13][CH:8]([C:5]1[CH:6]=[CH:7][C:2]([C:2]2[CH:7]=[CH:6][C:5]([CH:37]3[CH2:36][NH:35][CH2:34][CH2:33][N:32]3[C:30]([O:29][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:31])=[CH:4][CH:3]=2)=[CH:3][CH:4]=1)[C:9]([F:12])([F:11])[F:10])[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:20])#[N:24]

Participants

Conditions

Temperature: 85 °C

Procedure

To N2-[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N1-(cyanomethyl)-L-leucinamide (242 mg, 0.60 mmol), and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (220 mg, 0.72 mmol) in DME (3 mL) under dry nitrogen was added 2M aqueous sodium carbonate (0.9 mL, 1.8 mmol) followed by the catalyst PdCl2(dppf) (63 mg, 0.077 mmol). The reaction was heated to 85° C. for 18 hours. Water was added and the product was extracted with EtOAc, the organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by chromatography using EtOAc in hexane to afford tert-butyl (4′-{1-[((1S)-1-{[(cyanomethyl)amino]carbonyl}-3-methylbutyl)amino]-2,2,2-trifluoroethyl}-1,1′-biphenyl-4-yl)-1-piperazinecarboxylate.

Workup

extractionthe product was extracted with EtOAc
dry with materialthe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo
customThe crude product was purified by chromatography

Sources & evidence

ORD record: ord-92670791a0384fe69eb6874ba4e08076
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772336B2

Reaction notes

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