Chloroform → HCID 89783540, compound

HRID 1056329Notes

Reaction equation

HRID 1056329 reaction equation
[CH3:1][C@@H:2]1[C:6]2[NH:7][C:8]([C:10]3[CH:19]=[CH:18][CH:17]=[C:16]4[C:11]=3[N:12]=[C:13]([NH:21][C:22]3([CH3:25])[CH2:24][CH2:23]3)[C:14]([CH3:20])=[N:15]4)=[CH:9][C:5]=2[C:4](=[O:26])[NH:3]1.C(Cl)(Cl)[Cl:28]>>[Cl:28][C:9]1[C:5]2[C:4](=[O:26])[NH:3][C@H:2]([CH3:1])[C:6]=2[NH:7][C:8]=1[C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[N:12]=[C:13]([NH:21][C:22]1([CH3:25])[CH2:23][CH2:24]1)[C:14]([CH3:20])=[N:15]2

Participants

3

Reactant 2

HCID 6212ChloroformHCID 71696700HCID 71696700, compound

Product 1

HCID 89783540HCID 89783540, compoundYield 82%

Conditions

Temperature
50 °C

Procedure

To a suspension of (R)-6-methyl-2-(2-methyl-3-((1-methylcyclopropyl)-amino)quinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (333) (160 mg, 0.46 mmol) in 5 mL of CHCl3 at RT was added n-chlorosuccinimide (73.8 mg, 0.55 mmol) and the mixture was stirred in an oil bath at 50° C. for 1.5 h. LCMS indicated 80% conversion. Additional n-chlorosuccinimide (21 mg, 1.55 mmol) was added and heating at 50° C. was continued for another 30 min. It was cooled to RT, treated with 5 mL of ice cold 0.5 N NaOH, and extracted with 25 mL of DCM followed by 25 mL of EtOAc. The combined organic extracts were concentrated and the residue was purified on a silica gel column (50% EtOAc in DCM followed by 5% MeOH in EtOAc) to give (R)-3-chloro-6-methyl-2-(2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (454) (145 mg, 82% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.97 (1H, br.), 8.26 (1H, dd, J=7.6, 1.2 Hz), 7.84 (1H, s), 7.72 (1H, dd, J=8.0, 1.2 Hz), 7.64 (1H, s), 7.43 (1H, t, J=7.8 Hz), 4.61 (1H, q, J=6.7 Hz), 2.45 (3H, s), 1.45 (3H, s), 1.37 (3H, d, J=6.7 Hz), 0.89 (2H, m), 0.75 (2H, m). m/z (ESI, +ve) 382.0 (M+H)+.

Workup

  1. temperatureheating at 50° C.
  2. waitwas continued for another 30 min
  3. temperatureIt was cooled to RT
  4. extractionextracted with 25 mL of DCM
  5. concentrationThe combined organic extracts were concentrated
  6. customthe residue was purified on a silica gel column (50% EtOAc in DCM followed by 5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-7d177367936b4807a9dd1e7a3f0d1560
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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