Potassium Phosphate, Tribasic → HCID 117610749, compound

HRID 588907Notes

Reaction equation

Br[C:2]1[C:3]([Cl:32])=[CH:4][C:5]([C:29](=[O:31])[NH2:30])=[C:6]([NH:8][CH2:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH:18]3[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:19]3)[CH2:14][CH2:13]2)=[O:11])[CH:7]=1.[CH:33]1(B(O)O)[CH2:35][CH2:34]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:29]([C:5]1[CH:4]=[C:3]([Cl:32])[C:2]([CH:33]2[CH2:35][CH2:34]2)=[CH:7][C:6]=1[NH:8][CH2:9][C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:19]2)[CH2:14][CH2:13]1)=[O:11])(=[O:31])[NH2:30]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of tert-butyl 3-(4-(2-((5-bromo-2-carbamoyl-4-chlorophenyl)amino)acetyl)piperazin-1-yl)azetidine-1-carboxylate (350 mg, 0.66 mmol) and cyclopropylboronic acid (226 mg, 2.64 mmol) in toluene (10 mL) and water (2 mL), Pd(OAc)2 (15 mg, 0.07 mmol), PCy3 (37 mg, 0.132 mmol) and K3PO4 (487 mg, 2.31 mmol) were added. The mixture was stirred at 80° C. for 16 h. The mixture was allowed to cool to RT and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (1-5% methanol/dichloroethane) to afford the desired product (150 mg, 46% yield) as a solid.

Workup

temperatureto cool to RT
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel (1-5% methanol/dichloroethane)

Sources & evidence

ORD record: ord-1c84a719448f42d8ae9c4856aa794b7c
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227978B2

Reaction notes

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