Boron tribromide → 1-(4-(2-(4-chloro-2-hydroxy-5-(2-Chlorophenyl)phenylamino)acetyl)piperazin-1-yl)prop-2-en-1-one

HRID 588781Notes

Reaction equation

HRID 588781 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[Cl:14])=[CH:6][C:5]([NH:15][CH2:16][C:17]([N:19]2[CH2:24][CH2:23][N:22]([C:25](=[O:28])[CH:26]=[CH2:27])[CH2:21][CH2:20]2)=[O:18])=[C:4]([O:29]C)[CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[Cl:14])=[CH:6][C:5]([NH:15][CH2:16][C:17]([N:19]2[CH2:24][CH2:23][N:22]([C:25](=[O:28])[CH:26]=[CH2:27])[CH2:21][CH2:20]2)=[O:18])=[C:4]([OH:29])[CH:3]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 90462972K-Ras G12C-IN-1

Product 1

HCID 904636311-(4-(2-(4-chloro-2-hydroxy-5-(2-Chlorophenyl)phenylamino)acetyl)piperazin-1-yl)prop-2-en-1-oneYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(4-(2-(4-chloro-5-(2-Chlorophenyl)-2-methoxyphenylamino)acetyl)piperazin-1-yl)prop-2-en-1-one (70 mg, 0.147 mmol) in DCM (15 mL)-78° C. under argon, BBr3 (187 mg, 0.754 mmol) was added. The mixture was stirred at room temperature for 1 h. The mixture was poured into ice water and extracted ethyl acetate. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=40:1) to afford the desired product (15 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ: 10.08 (s, 1H), 7.53-7.51 (m, 1H), 7.41-7.37 (m, 2H), 7.30-7.28 (m, 1H), 6.84-6.77 (m, 2H), 6.48 (s, 1H), 6.12 (dd, J=2.4, 16.4 Hz, 1H), 5.70 (dd, J=2.0, 10.4 Hz, 1H), 5.24 (t, J=4.0 Hz, 1H), 3.90 (d, J=4.4 Hz, 2H), 3.56-3.49 (m, 8H). ESI-MS m/z: 434.2[M+H]+.

Workup

  1. extractionextracted ethyl acetate
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=40:1)

Sources & evidence

ORD record
ord-34af5d0005af41d98567f5d6fb113df9
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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