Triethylamine → HCID 89793964, compound

HRID 1056377Notes

Reaction equation

HRID 1056377 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:9]2[C:10]([CH3:29])=[N:11][C:12]3[C:17]([N:18]=2)=[C:16]([C:19]2[NH:23][C:22]4[C@@H:24]([CH3:28])[NH:25][C:26](=[O:27])[C:21]=4[CH:20]=2)[CH:15]=[CH:14][CH:13]=3)[CH2:3]1.[CH3:30][S:31](Cl)(=[O:33])=[O:32].C(N(CC)CC)C>C(Cl)Cl>[CH3:29][C:10]1[C:9]([NH:8][C@H:4]2[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][S:31]([CH3:30])(=[O:33])=[O:32])[CH2:3]2)=[N:18][C:17]2[C:12]([N:11]=1)=[CH:13][CH:14]=[CH:15][C:16]=2[C:19]1[NH:23][C:22]2[C@@H:24]([CH3:28])[NH:25][C:26](=[O:27])[C:21]=2[CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 89783660HCID 89783660, compound

Product 1

HCID 89793964HCID 89793964, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of (R)-2-(3-(((1S,3R)-3-aminocyclohexyl)amino)-2-methylquinoxalin-5-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (483, 52 mg, 0.133 mmol), methanesulfonyl chloride (41.4 μL, 0.533 mmol), and triethylamine (74.2 μL, 0.533 mmol) in DCM (1.33 mL) was stirred at 0° C. for 5 min; the reaction mixture was warmed to RT and stir for 1 h when product was observed via LCMS. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aqueous NaHCO3 (2×75 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was loaded onto the column and was purified via automated flash chromatography (silica gel) with 0-5% 2 M ammonia in MeOH/DCM to give N-((1R,3S)-3-((3-methyl-8-((R)-6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinoxalin-2-yl)amino)cyclohexyl)methanesulfonamide (489, 6 mg, 0.013 mmol, 10% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.24-1.36 (m, 2H) 1.37-1.51 (m, 2H) 1.59 (d, J=6.65 Hz, 3H) 1.99-2.06 (m, 1H) 2.16-2.23 (m, 1H) 2.39 (d, J=11.15 Hz, 1H) 2.52-2.57 (m, 1H) 2.59 (s, 3H) 3.00 (s, 3H) 3.48-3.59 (m, 1H) 3.99-4.10 (m, 1H) 4.54 (d, J=7.04 Hz, 1H) 4.68 (q, J=6.98 Hz, 1H) 4.97 (d, J=6.65 Hz, 1H) 5.68 (s, 1H) 6.92 (d, J=1.37 Hz, 1H) 7.42 (t, J=7.82 Hz, 1H) 7.69-7.74 (m, 1H) 7.91-7.97 (m, 1H) 12.29 (br. s., 1H). MS (ESI, pos. ion) m/z: 469.1 (M+1).

Workup

  1. temperaturethe reaction mixture was warmed to RT
  2. stirringstir for 1 h when product
  3. additionadded to a separatory funnel
  4. washwashed with saturated aqueous NaHCO3 (2×75 mL)
  5. customthe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customwas purified

Sources & evidence

ORD record
ord-95383527ac5b4ce5b54e39f2f09d2885
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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