Methanesulfonyl chloride → HCID 89783940, compound

HRID 1056337Notes

Reaction equation

HRID 1056337 reaction equation
[C:1]([NH:5][C:6]1[C:7]([CH3:28])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:20][C:19]3[CH:21]([CH2:25][CH2:26]O)[NH:22][C:23](=[O:24])[C:18]=3[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].CS(Cl)(=O)=O.[N-:34]=[N+:35]=[N-:36].[Na+]>C(Cl)Cl.CCOC(C)=O>[N:34]([CH2:26][CH2:25][CH:21]1[C:19]2[NH:20][C:16]([C:13]3[CH:12]=[CH:11][CH:10]=[C:9]4[C:14]=3[N:15]=[C:6]([NH:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:7]([CH3:28])=[N:8]4)=[CH:17][C:18]=2[C:23](=[O:24])[NH:22]1)=[N+:35]=[N-:36]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 89784087HCID 89784087, compound

Product 1

HCID 89783940HCID 89783940, compoundYield 61.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6-(2-hydroxyethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (462) (149 mg, 0.39 mmol) in 5 mL of DCM at 0° C. was added TEA (0.27 mL, 1.96 mmol) followed by methanesulfonyl chloride (33.4 μL, 0.43 mmol). It was stirred at 0° C. for 30 min, diluted with 30 mL of DCM, washed sequentially with 5 mL of water, 5 mL of sat NaHCO3 and 5 mL of brine. The DCM solution was dried over Na2SO4 and concentrated. The brown residue was dissolved in 1 mL of DMF and treated with sodium azide (80 mg, 1.24 mmol). The mixture was heated in an oil bath at 70° C. for 45 min. It was diluted with EtOAc (50 mL) and filtered. The filtrate was washed with 2×5 mL of water. The EtOAc solution was concentrated and purified on a silica gel column (2-8% MeOH in DCM) to give 6-(2-azidoethyl)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (463a, 97 mg, 0.24 mmol, 61% yield). m/z (ESI, +ve) 405 (M+H)+. To a solution of 6-(2-azidoethyl)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrolo-4(1H)-one (463a, 97 mg, 0.24 mmol) in 3 mL of THF and water (43.2 μl, 2.39 mmol) at RT was added trimethylphosphine (0.36 mL of 1 M in THF, 0.36 mmol). It was stirred at RT for 30 min, then diluted with 50 mL of EtOAc, and washed with 5 mL of water. The organic layer was concentrated and the residue was purified on a silica gel column (5% MeOH in DCM followed by 5% of 2 M NH3 in MeOH in DCM) to provide 6-(2-aminoethyl)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (463) (68 mg, 0.18 mmol, 75% yield) as a brown amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.81 (1H, dd, J=7.4, 1.4 Hz), 7.71 (1H, s), 7.57-7.67 (1H, m), 7.35 (1H, t, J=7.7 Hz), 6.84 (1H, s), 5.99 (1H, s), 4.57 (1H, dd, J=8.4, 4.1 Hz), 3.41 (3H, br.), 2.64-2.77 (2H, m), 2.56 (3H, s), 1.92 (1H, dd, J=13.3, 4.3 Hz), 1.57-1.65 (1H, m), 1.55 (9H, s). m/z 379.1 (ESI, +ve) (M+H)+.

Workup

  1. washwashed sequentially with 5 mL of water, 5 mL of sat NaHCO3 and 5 mL of brine
  2. dry with materialThe DCM solution was dried over Na2SO4
  3. concentrationconcentrated
  4. dissolutionThe brown residue was dissolved in 1 mL of DMF
  5. temperatureThe mixture was heated in an oil bath at 70° C. for 45 min
  6. filtrationfiltered
  7. washThe filtrate was washed with 2×5 mL of water
  8. concentrationThe EtOAc solution was concentrated
  9. custompurified on a silica gel column (2-8% MeOH in DCM)

Sources & evidence

ORD record
ord-88dbdfdca2194dfa9e0a75dfbfc1d4c7
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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