Sodium Carbonate → 6-isopropyl-9-(1-methyl-1H-pyrazol-4-yl)benzo[c]-1,6-naphthyridin-1(2H)-one

HRID 2193015Notes

Reaction equation

HRID 2193015 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:15]([CH3:17])[CH3:16])=[N:7][C:8]3[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.CN(C=O)C>[CH:15]([C:6]1[C:5]2[CH:18]=[CH:19][C:2]([C:24]3[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=3)=[CH:3][C:4]=2[C:13]2[C:12](=[O:14])[NH:11][CH:10]=[CH:9][C:8]=2[N:7]=1)([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 593756889-bromo-6-isopropylbenzo[c]-1,6-naphthyridin-1(2H)-one

Product 1

HCID 593753866-isopropyl-9-(1-methyl-1H-pyrazol-4-yl)benzo[c]-1,6-naphthyridin-1(2H)-one

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

9-bromo-6-isopropylbenzo[c]-1,6-naphthyridin-1(2H)-one (50 mg, 0.16 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (66 mg, 0.32 mmol), PdCl2(dppf)-CH2Cl2 adduct (26 mg, 0.032 mmol), DMF (1.7 ml), and 2 M aqueous sodium carbonate (0.16 ml, 0.32 mmol) were combined in a microwave vial and sparged with argon for 5 minutes. The reaction mixture was heated in a microwave reactor at 100° C. for 30 min. The reaction mixture was diluted with MeOH and purified directly by preparative reverse phase HPLC eluting with an acetonitrile/water (with 0.05% TFA modifier) gradient to afford 6-isopropyl-9-(1-methyl-1H-pyrazol-4-yl)benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO D-6) δ 11.69 (br d, 1H), 10.20 (d, 1H), 8.42 (d, 1H), 8.32 (s, 1H), 7.97 (s, 1H), 7.94 (dd, 1H), 7.51 (t, 1H), 6.73 (d, 1H), 4.06 (septet, 1H), 3.92 (s, 3H), 1.37 (d, 6H). LRMS (ESI) calc'd for (C19H18N4O) [M+H]+, 319.1; found 319.1.

Workup

  1. customsparged with argon for 5 minutes
  2. additionThe reaction mixture was diluted with MeOH
  3. custompurified directly by preparative reverse phase HPLC
  4. washeluting with an acetonitrile/water (with 0.05% TFA modifier) gradient

Sources & evidence

ORD record
ord-b5d244367b124861a0a08d49d3157e37
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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