1,2-Diaminocyclohexane → 2-((3-fluorobenzyl)oxy)-6-(5-fluoropyridin-2-yl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one

HRID 533149Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[CH2:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:13](=[O:17])[NH:12][CH2:11][CH2:10][C:9]=2[N:8]=1.Br[C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=1.NC1CCCCC1N.[Li+].[Cl-]>[Cu]I.CCOC(C)=O.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[CH2:5][O:6][C:7]1[CH:16]=[CH:15][C:14]2[C:13](=[O:17])[N:12]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=3)[CH2:11][CH2:10][C:9]=2[N:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

2-((3-fluorobenzyl)oxy)-7,8-dihydro-1,6-naphthyridin-5(6H)-one (20 mg, 0.07 mmol) was dissolved into DMF (1 mL) and treated with 2-bromo-5-fluoropyridine (17 mg, 0.1 mmol), 1,2-diaminocyclohexane (4 mg, 0.04 mmol) and CuI (2 mg, 0.01 mmol). The reaction was stirred at 100° C. over 72 h and then poured onto 3M LiCl and EtOAc (5 mL each). The organic layers were dried over Na2SO4, concentrated and the residue purified RP-HPLC to give the compound, 2-((3-fluorobenzyl)oxy)-6-(5-fluoropyridin-2-yl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one. LC-MS (M+H)=368.1.

Workup

dry with materialThe organic layers were dried over Na2SO4
concentrationconcentrated
customthe residue purified RP-HPLC

Sources & evidence

ORD record: ord-f91df01b97c14eaea548c98c6b162e2f
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853237B2

Reaction notes

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