1,4-Dioxane → 6-[(2,2-dimethylpropyl)amino]-9-fluorobenzo[c]-1,6-naphthyridin-1(2H)-one

HRID 2192964Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:5]=1[C:6](Cl)=[N:7]2.[CH3:18][C:19]([CH3:23])([CH3:22])[CH2:20][NH2:21].[O:24]1CCOCC1>>[CH3:18][C:19]([CH3:23])([CH3:22])[CH2:20][NH:21][C:6]1[C:5]2[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:4]=2[C:3]2[C:2](=[O:24])[NH:11][CH:10]=[CH:9][C:8]=2[N:7]=1

Participants

Reactant 3

HCID 312751,4-Dioxane

HCID 79882Neopentylamine

HCID 59375375HCID 59375375, compound

Product 1

HCID 250957596-[(2,2-dimethylpropyl)amino]-9-fluorobenzo[c]-1,6-naphthyridin-1(2H)-one

Conditions

Temperature: 100 °C

Procedure

To a solution of 1,6-dichloro-9-fluorobenzo[c]-1,6-naphthyridine (20 mg, 0.075 mmol) in dioxane (1.5 mL) was added 2,2-dimethylpropan-1-amine (39 mg, 0.45 mmol) and heated in a microwave reactor at 100° C. for 30 to 50 min. The solution was concentrated and converted to 6-[(2,2-dimethylpropyl)amino]-9-fluorobenzo[c]-1,6-naphthyridin-1(2H)-one in a similar manner exemplified in the synthesis of 9-bromo-6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}benzo[c]-1,6-naphthyridin-1(2H)-one (Method A, Step 2). 1H NMR (600 MHz, CD3OD) δ 9.65 (dd, 1H), 8.60 (dd, 1H), 7.60 (d, 1H), 7.58 (m, 1H), 6.95 (d, 1H), 3.70 (s, 2H), 1.10 (s, 9H). LRMS (ESI) calc'd for (C17H19FN3O) [M+H]+, 300.15; found 300.1.

Workup

concentrationThe solution was concentrated
customexemplified in the synthesis of 9-bromo-6-{[(1R)-2-methyl-1-(trifluoromethyl)propyl]amino}benzo[c]-1,6-naphthyridin-1(2H)-one (Method A, Step 2)

Sources & evidence

ORD record: ord-529e09f613ac4c0cae98e521a435629c
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329722B2

Reaction notes

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