HCID 71730635, compound → HCID 71730636, compound

HRID 1056228Notes

Reaction equation

HRID 1056228 reaction equation
Br[C:2]1[C:6]2[C:7](=[O:11])[NH:8][CH2:9][CH2:10][C:5]=2[NH:4][C:3]=1[C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[N:14]=[C:15]([NH:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:16]([CH3:22])=[N:17]2.[CH3:28][Zn]C>O1CCOCC1.C(Cl)Cl>[C:24]([NH:23][C:15]1[C:16]([CH3:22])=[N:17][C:18]2[C:13]([N:14]=1)=[C:12]([C:3]1[NH:4][C:5]3[CH2:10][CH2:9][NH:8][C:7](=[O:11])[C:6]=3[C:2]=1[CH3:28])[CH:21]=[CH:20][CH:19]=2)([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 2

HCID 71730635HCID 71730635, compoundHCID 178477796HCID 178477796, compound

Product 1

HCID 71730636HCID 71730636, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-bromo-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (349) (61 mg, 0.14 mmol), dimethylzinc in hexanes (0.39 mL of 10% wt. in hexanes, 0.570 mmol, Strem Chemicals, Inc.,), and (A-Phos)2PdCl2 (10 mg, 0.014 mmol) in dioxane (1.42 mL) was stirred at 80° C. for 2 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 aq. NaHCO3 (2×75 mL) before the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 1-4% of 2 M NH3 in MeOH/DCM to give impure 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-3-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one contaminated with starting material. The impure product was purified via SFC [IC (3×15 cm, 5 μm), 60% 0.2% DEA in MeOH: EtOH: isopropanol (1:1:1) (NH4OH)/CO2, 100 bar; 65 mL/min, 220 nm; inj vol.: 1.5 mL, 3.5 mg/mL in MeOH] to give 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-3-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (350, 10 mg, 0.028 mmol, 19% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.60 (s, 9H) 2.55 (s, 3H) 2.69 (s, 3H) 2.95 (t, J=6.85 Hz, 2H) 3.61 (td, J=6.85, 2.54 Hz, 2H) 4.79 (s, 1H) 5.18 (br. s., 1H) 7.42 (t, J=7.92 Hz, 1H) 7.68 (dd, J=8.12, 1.27 Hz, 1H) 7.85 (dd, J=7.53, 1.08 Hz, 1H) 11.62 (br. s., 1H). MS (ESI, pos. ion) m/z: 364.2 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aq. NaHCO3 (2×75 mL) before the organic layer
  3. customwas separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customwas purified

Sources & evidence

ORD record
ord-024ded10ec964ec5aca7907dd95a6a75
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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