Boron Trichloride → HCID 78161917, compound

HRID 1056238Notes

Reaction equation

HRID 1056238 reaction equation
C([O:8][CH2:9][CH:10]1[C:14]2[NH:15][C:16]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[N:20]=[C:21]([NH:29][C:30]3([CH3:33])[CH2:32][CH2:31]3)[C:22]([CH3:28])=[N:23]4)=[CH:17][C:13]=2[C:12](=[O:34])[NH:11]1)C1C=CC=CC=1.B(Cl)(Cl)Cl>C(Cl)Cl>[OH:8][CH2:9][CH:10]1[C:14]2[NH:15][C:16]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[N:20]=[C:21]([NH:29][C:30]3([CH3:33])[CH2:31][CH2:32]3)[C:22]([CH3:28])=[N:23]4)=[CH:17][C:13]=2[C:12](=[O:34])[NH:11]1

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 89784612HCID 89784612, compound

Product 1

HCID 78161917HCID 78161917, compoundYield 71.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 25-mL round-bottomed flask was added 6-((benzyloxy)methyl)-2-(2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (355) (0.12 g, 0.27 mmol) and DCM (3 mL). The reaction mixture was cooled to −78° C. and under a N2 atmosphere boron trichloride (0.54 mL, 0.54 mmol, 1 M in DCM) (Sigma-Aldrich Chemical Company, Inc.) was added dropwise. The reaction mixture was stirred at −78° C. for 30 min and at 0° C. for 30 min. The reaction was quenched by the addition of NaHCO3 (100 mg in MeOH, 3 mL) and the solvent was removed under vacuum. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluted with a gradient of 2-7% MeOH in DCM to provide 6-(hydroxymethyl)-2-(2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (360) (70 mg, 71% yield, 50% ee) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 8.05 (dd, J=1.17, 7.63 Hz, 1H), 7.68 (s, 1H), 7.63 (s, 1H), 7.61 (dd, J=1.17, 8.02 Hz, 1H), 7.37 (t, J=7.82 Hz, 1H), 7.03 (d, J=1.17 Hz, 1H), 5.20 (t, J=5.48 Hz, 1H), 4.54 (t, J=6.06 Hz, 1H), 3.66 (td, J=5.55, 10.61 Hz, 1H), 3.45-3.57 (m, 1H), 2.51 (s, 3H), 1.54 (s, 3H), 0.88-1.01 (m, 4H). m/z (ESI, +ve) 364.1 (M+H)+.

Workup

  1. additionwas added dropwise
  2. customThe reaction was quenched by the addition of NaHCO3 (100 mg in MeOH, 3 mL)
  3. customthe solvent was removed under vacuum
  4. customThe crude material was absorbed onto a plug of silica gel
  5. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  6. washeluted with a gradient of 2-7% MeOH in DCM

Sources & evidence

ORD record
ord-596d91dba7ee4ca099be10050614fd06
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…