Diisopropylethylamine → 1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one

HRID 1056318Notes

Reaction equation

HRID 1056318 reaction equation
Cl.N[C@@H]1C[C@H](NC2C(C)=NC3C(N=2)=C([C:18]2[NH:26][C:25]4[CH2:24][CH2:23][NH:22][C:21](=[O:27])[C:20]=4[CH:19]=2)C=CC=3)C1.ClC(Cl)(Cl)S(OCC(F)(F)F)(=O)=O.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[NH:26]1[C:25]2[CH2:24][CH2:23][NH:22][C:21](=[O:27])[C:20]=2[CH:19]=[CH:18]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonateHCID 178432139HCID 178432139, compound

Product 1

HCID 220385131H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-oneYield 39.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2-(3-((cis-3-aminocyclobutyl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one hydrochloride (Example 435; 27.4 mg, 0.069 mmol), 2,2,2-trifluoroethyl trichloromethanesulfonate (Oakwood Products, Inc., West Columbia, S.C.; 0.073 mL, 0.446 mmol), and DIPEA (0.120 mL, 0.686 mmol) in a mixture of THF (1.0 mL) and DMF (1.0 mL) was heated in a sealed flask at 110° C. for 30 min. The reaction mixture was then cooled to RT, concentrated onto silica gel, and chromatographically purified (silica gel, 10-100% (3:1 EtOAc-EtOH)/hexanes). The product-containing fractions were concentrated in vacuo, and the residue was taken up in 5% MeOH/DCM (40 mL), sequentially washed with half-saturated aqueous NaHCO3 (30 mL) and water (30 mL), dried over Na2SO4, filtered and concentrated in vacuo to provide 2-(2-methyl-3-(1s,3s)-3-((2,2,2-trifluoroethyl)amino)cyclobutyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (11.8 mg, 0.027 mmol, 39% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 12.57 (1H, br. s.), 7.94 (1H, dd, J=7.5, 1.1 Hz), 7.68 (1H, dd, J=8.1, 1.1 Hz), 7.41 (1H, t, J=7.8 Hz), 7.14 (1H, d, J=2.2 Hz), 5.31 (1H, br. s.), 5.16 (1H, d, J=4.7 Hz), 4.13-4.27 (1H, m), 3.68 (2H, td, J=6.9, 2.4 Hz), 3.32-3.43 (1H, m), 3.23 (2H, q, J=9.4 Hz), 3.01-3.08 (2H, m), 2.99 (2H, t, J=6.8 Hz), 2.59 (3H, s), 1.80-1.94 (2H, m). 19F NMR (376 MHz, CDCl3) δ ppm −71.65 (3F, br. s.). m/z (ESI, +ve) 445.0 (M+H)+.

Workup

  1. temperatureThe reaction mixture was then cooled to RT
  2. concentrationconcentrated onto silica gel
  3. customchromatographically purified (silica gel, 10-100% (3:1 EtOAc-EtOH)/hexanes)
  4. concentrationThe product-containing fractions were concentrated in vacuo
  5. washsequentially washed with half-saturated aqueous NaHCO3 (30 mL) and water (30 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-463b9063923b4b9ca969934367074f59
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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