HCID 117610822, compound → HCID 117610829, compound

HRID 588903Notes

Reaction equation

Br[C:2]1[C:3]([Cl:32])=[CH:4][C:5]([O:30][CH3:31])=[C:6]([NH:8][C@@H:9]([CH3:29])[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.[Zn](CC)[CH2:34][CH3:35]>C1COCC1.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]>[Cl:32][C:3]1[C:2]([CH2:34][CH3:35])=[CH:7][C:6]([NH:8][C@@H:9]([CH3:29])[C:10]([N:12]2[CH2:13][CH2:14][N:15]([CH:18]3[CH2:19][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[CH2:21]3)[CH2:16][CH2:17]2)=[O:11])=[C:5]([O:30][CH3:31])[CH:4]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (S)-tert-butyl 3-(4-(2-((5-bromo-4-chloro-2-methoxyphenyl)amino)propanoyl)piperazin-1-yl)azetidine-1-carboxylate (400 mg, 0.75 mmol), PdCl2(dppf) (95 mg, 0.13 mmol) in THF (20 mL) at RT, Et2Zn (2.86 mL, 2.86 mmol, 1.0 M in hexane) was added. The resulting mixture was stirred under argon at 80° C. for 4 h and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (methanol/dichloroethane=1:80) to afford the desired product (250 mg, 69% yield). ESI-MS m/z: 481.2[M+H]+.

Workup

custompartitioned between ethyl acetate and water
washThe organic layer was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel (methanol/dichloroethane=1:80)

Sources & evidence

ORD record: ord-869e53eb53434ed7b853b7bbfae5e5d5
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227978B2

Reaction notes

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