1-Methylcyclobutan-1-amine hydrochloride → 8-Bromo-7-fluoro-3-methyl-N-(1-methylcyclobutyl)quinoxalin-2-amine

HRID 1056256Notes

Reaction equation

HRID 1056256 reaction equation
BrC1C(F)=CC=C2C=1N=C(NC(C)(C)C)C(C)=N2.BrC1C(F)=CC=C2C=1NC(=O)C(C)=N2.Cl.CC1(N)CCC1.CC1(C)C(C)(C)OB([C:48]2[NH:56][C:55]3[CH2:54][CH2:53][NH:52][C:51](=[O:57])[C:50]=3[CH:49]=2)O1.[Br:59][C:60]1[C:61]([F:77])=[CH:62][CH:63]=[C:64]2[C:69]=1[N:68]=[C:67]([NH:70][C:71]1([CH3:75])[CH2:74][CH2:73][CH2:72]1)[C:66]([CH3:76])=[N:65]2>CS(C)=O>[Br:59][C:60]1[C:61]([F:77])=[CH:62][CH:63]=[C:64]2[C:69]=1[N:68]=[C:67]([NH:70][C:71]1([CH3:75])[CH2:74][CH2:73][CH2:72]1)[C:66]([CH3:76])=[N:65]2.[F:77][C:61]1[C:60]([C:48]2[NH:56][C:55]3[CH2:54][CH2:53][NH:52][C:51](=[O:57])[C:50]=3[CH:49]=2)=[C:69]2[C:64](=[CH:63][CH:62]=1)[N:65]=[C:66]([CH3:76])[C:67]([NH:70][C:71]1([CH3:75])[CH2:72][CH2:73][CH2:74]1)=[N:68]2

Participants

8

Reactant 5

HCID 183324491-Methylcyclobutan-1-amine hydrochlorideHCID 897819348-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amineHCID 897823698-Bromo-7-fluoro-3-methyl-N-(1-methylcyclobutyl)quinoxalin-2-amineHCID 897834962-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-oneHCID 897842068-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one

Product 2

HCID 897823698-Bromo-7-fluoro-3-methyl-N-(1-methylcyclobutyl)quinoxalin-2-amineYield 88%HCID 897834262-(6-Fluoro-2-methyl-3-((1-methylcyclobutyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 42%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

8-Bromo-7-fluoro-3-methyl-N-(1-methylcyclobutyl)quinoxalin-2-amine (376a) (620 mg, 1.91 mmol, 88% yield) as a light brown viscous oil was prepared according to the procedure described for Intermediate 605a, using 5-bromo-3-chloro-6-fluoro-2-methylquinoxaline (600) (600 mg, 2.18 mmol), TEA (0.76 mL, 5.44 mmol) and 1-methylcyclobutanamine hydrochloride (Matrix Scientific Columbia, S.C.) (500 mg, 4.11 mmol) in DMSO (5.0 mL) as the starting materials. 1H NMR (400 MHz, CDCl3) δ ppm 7.71 (1H, dd, J=9.0, 5.7 Hz), 7.13 (1H, t, J=8.6 Hz), 5.01 (1H, br. s.), 2.51 (3H, s), 2.42-2.51 (2H, m), 2.30 (2H, dddd, J=9.8, 7.3, 4.6, 2.6 Hz), 1.90-2.01 (2H, m), 1.73 (3H, s). 19F NMR (377 MHz, CDCl3) δ ppm −103.73 (1F, s). m/z (ESI, +ve ion) 324.0/326.0 (M+H)+. 2-(6-Fluoro-2-methyl-3-((1-methylcyclobutyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (269 mg, 0.71 mmol, 42% yield) as an amorphous yellow solid was prepared according to the procedure described for Example 370, using 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (609) (800 mg, 3.05 mmol), and 8-bromo-7-fluoro-3-methyl-N-(1-methylcyclobutyl)quinoxalin-2-amine (376a) (549 mg, 1.70 mmol) as the starting materials. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.53 (1H, br. s.), 7.61 (1H, dd, J=9.0, 5.9 Hz), 7.29 (1H, dd, J=11.5, 9.0 Hz), 7.21 (1H, s), 7.05 (1H, br. s.), 6.85 (1H, dd, J=4.1, 2.0 Hz), 3.45 (2H, td, J=6.9, 2.4 Hz), 2.93 (2H, t, J=6.8 Hz), 2.54 (3H, s), 2.38-2.47 (2H, m), 2.13-2.24 (2H, m), 1.82-1.97 (2H, m), 1.66 (3H, s). 19F NMR (377 MHz, DMSO-d6) δ ppm −109.90 (1F, s). m/z (ESI, +ve ion) 380.1 (M+H)+.

Sources & evidence

ORD record
ord-422dd7dfdb114f69a6434195214cb1f1
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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