Ethyl Acetate → HCID 178432141, compound

HRID 1056316Notes

Reaction equation

HRID 1056316 reaction equation
F[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.Cl.[NH2:24][C@@H:25]1[CH2:28][C@H:27]([OH:29])[CH2:26]1.CCN(C(C)C)C(C)C.CCOC(C)=O>CS(C)=O.O.CO.C(Cl)Cl>[OH:29][C@@H:27]1[CH2:28][C@H:25]([NH:24][C:2]2[C:3]([CH3:22])=[N:4][C:5]3[C:10]([N:11]=2)=[C:9]([C:12]2[NH:20][C:19]4[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=4[CH:13]=2)[CH:8]=[CH:7][CH:6]=3)[CH2:26]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneHCID 178479286HCID 178479286, compound

Product 1

HCID 178432141HCID 178432141, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
23 °C

Procedure

A solution of 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 85.0 mg, 0.287 mmol), cis-3-aminocyclobutanol hydrochloride (46.2 mg, 0.374 mmol), and DIPEA (0.150 mL, 0.861 mmol) in DMSO (2.0 mL) was stirred under argon at 100° C. for 30 min. The reaction mixture was subsequently cooled to 23° C. and diluted with water (10 mL). The resulting mixture was extracted with 5% MeOH/DCM (2×30 mL), and the combined extracts were sequentially washed with water (2×10 mL) and then concentrated onto silica gel. Chromatographic purification (silica gel, 50-100% EtOAc/Hexanes, then 100% EtOAc, then 0-10% MeOH/DCM) provided 2-(3-((cis-3-hydroxycyclobutyl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (9.3 mg, 0.026 mmol, 11% yield) as a yellow solid. The combined aqueous layers from the aqueous workup were filtered through a fine glass frit, and the collected solid was sequentially washed with water (40 mL) and ether (30 mL), then dried in vacuo to provide additional 2-(3-((cis-3-hydroxycyclobutyl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (92.2 mg, 0.254 mmol, 88% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.35 (1H, br. s.), 7.90 (1H, d, J=8.0 Hz), 7.56 (1H, d, J=7.6 Hz), 7.27-7.40 (2H, m), 7.09 (1H, br. s.), 6.95 (1H, br. s.), 5.18 (1H, d, J=6.3 Hz), 3.92-4.08 (1H, m), 3.41-3.50 (3H, m), 2.86-2.96 (2H, m), 2.74-2.86 (2H, m), 2.55 (3H, br. s.), 1.93-2.07 (2H, m). m/z (ESI, +ve) 364.0 (M+H)+.

Workup

  1. extractionThe resulting mixture was extracted with 5% MeOH/DCM (2×30 mL)
  2. washthe combined extracts were sequentially washed with water (2×10 mL)
  3. concentrationconcentrated onto silica gel
  4. customChromatographic purification (silica gel, 50-100% EtOAc/Hexanes

Sources & evidence

ORD record
ord-18ae49cdf3c04b30ac236daa12b3cadb
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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