Dichloromethane → HCID 178432140, compound

HRID 1056317Notes

Reaction equation

HRID 1056317 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:6][C@H:5]([NH:7][C:8]2[C:9]([CH3:28])=[N:10][C:11]3[C:16]([N:17]=2)=[C:15]([C:18]2[NH:26][C:25]4[CH2:24][CH2:23][NH:22][C:21](=[O:27])[C:20]=4[CH:19]=2)[CH:14]=[CH:13][CH:12]=3)[CH2:4]1.[CH3:29][S:30]([CH:33]=[CH2:34])(=[O:32])=[O:31].CCN(C(C)C)C(C)C.C(Cl)Cl>CC(O)C.CO>[NH3:2].[CH3:28][C:9]1[C:8]([NH:7][C@H:5]2[CH2:4][C@@H:3]([NH:2][CH2:34][CH2:33][S:30]([CH3:29])(=[O:32])=[O:31])[CH2:6]2)=[N:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[C:18]2[NH:26][C:25]3[CH2:24][CH2:23][NH:22][C:21](=[O:27])[C:20]=3[CH:19]=2)[N:10]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 19354Methyl vinyl sulfoneHCID 81531DiisopropylethylamineHCID 178432139HCID 178432139, compound

Product 2

HCID 222AmmoniaHCID 178432140HCID 178432140, compoundYield 169.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

A suspension 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; 20.6 mg, 0.052 mmol), methylvinylsulfone (Aldrich; 0.018 mL, 0.207 mmol), and DIPEA (0.036 mL, 0.207 mmol) in IPA (1.0 mL) was heated in a sealed vial at 120° C. for 15 min. The reaction mixture was then concentrated onto silica gel and chromatographically purified (silica gel, 100% EtOAc, then 0-10% (2M NH3 in MeOH)/DCM) to provide 2-(2-methyl-3-((cis-3-((2-(methylsulfonyl)ethyl)amino)cyclobutyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (20.5 mg, 0.044 mmol, 85% yield) as a yellow-orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.33 (1H, br. s.), 7.90 (1H, dd, J=7.5, 1.1 Hz), 7.56 (1H, dd, J=8.1, 1.1 Hz), 7.36 (1H, d, J=5.0.7 Hz), 7.32 (1H, t, J=7.8 Hz), 7.10 (1H, d, J=2.0 Hz), 6.95 (1H, s), 4.11-4.22 (1H, m), 3.46 (2H, td, J=6.8, 2.4 Hz), 3.28-3.30 (1H, m), 3.19-3.25 (2H, m), 3.05-3.15 (1H, m), 3.02 (3H, s), 2.92 (4H, t, J=6.7 Hz), 2.73-2.82 (2H, m), 2.55 (3H, s), 1.82-1.92 (2H, m). m/z (ESI, +ve) 469.0 (M+H)+.

Workup

  1. concentrationThe reaction mixture was then concentrated onto silica gel
  2. customchromatographically purified (silica gel, 100% EtOAc

Sources & evidence

ORD record
ord-eca960072d064373b6d113e15a1f6a47
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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