Triethylamine → K-Ras G12C-IN-1

HRID 588780Notes

Reaction equation

HRID 588780 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([Cl:26])=[CH:10][C:11]([O:24][CH3:25])=[C:12]([NH:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)=[O:17])[CH:13]=1.CCN(CC)CC.[C:34](Cl)(=[O:37])[CH:35]=[CH2:36]>C(Cl)Cl>[Cl:26][C:9]1[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[CH:13][C:12]([NH:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:34](=[O:37])[CH:35]=[CH2:36])[CH2:20][CH2:19]2)=[O:17])=[C:11]([O:24][CH3:25])[CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 13140Acryloyl chlorideHCID 1176104652-(5-(2-Chloropheny)-4-chloro-2-methoxyphenylamino)-1-(piperazin-1-yl)ethanone

Product 1

HCID 90462972K-Ras G12C-IN-1Yield 58.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the crude 2-(5-(2-Chlorophenyl)-4-chloro-2-methoxyphenylamino)-1-(piperazin-1-yl)ethanone (0.304 mmol) and Et3N in DCM (5 mL) at 0° C., acryloyl chloride (27.5 mg, 0.304 mmol) was slowly added and the resulting mixture was stirred at room temperature for 1 h. The mixture was quenched with saturated NaHCO3 solution and extracted with DCM. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to afford the desired product (80 mg, 58.7% yield, 2 steps). 1H NMR (400 MHz, DMSO-d6) δ: 7.55-7.52 (m, 1H), 7.45-7.39 (m, 2H), 7.32-7.29 (m, 1H), 6.97 (s, 1H), 6.80 (dd, J=10.4, 16.4 Hz, 1H), 6.54 (s, 1H), 6.12 (dd, J=2.0, 16.8 Hz, 1H), 5.70 (dd, J=2.0, 10.4 Hz, 1H), 5.35 (bs., 1H), 3.93 (d, J=4.0 Hz, 2H), 3.89 (s, 1H), 3.55-3.49 (m, 8H). ESI-MS m/z: 448.2[M+H]+.

Workup

  1. customThe mixture was quenched with saturated NaHCO3 solution
  2. extractionextracted with DCM
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-224f6cf55e604052802500b8c4473652
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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