Morpholine → 6-isopropyl-9-(morpholin-4-ylcarbonyl)benzo[c]-1,6-naphthyridin-1(2H)-one

HRID 2193016Notes

Reaction equation

HRID 2193016 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.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[H+].[B-](F)(F)(F)F.C1CCN2C(=NCCC2)CC1.[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1.[O:56]1CCOC[CH2:57]1>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[CH:15]([C:6]1[C:5]2[CH:18]=[CH:19][C:2]([C:57]([N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[O:56])=[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

8

Reactant 5

HCID 8083MorpholineHCID 312751,4-DioxaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 593756889-bromo-6-isopropylbenzo[c]-1,6-naphthyridin-1(2H)-oneHCID 86626500tri-(t-butyl)phosphonium HBF4

Product 1

HCID 593756236-isopropyl-9-(morpholin-4-ylcarbonyl)benzo[c]-1,6-naphthyridin-1(2H)-one

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Conditions

Temperature
100 °C

Procedure

9-bromo-6-isopropylbenzo[c]-1,6-naphthyridin-1(2H)-one (50 mg, 0.16 mmol), molybdenum hexacarbonyl (0.042 g, 0.16 mmol), trans-di-mu-acetatobis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) (7.4 mg, 7.9 mmol), and tri-(t-butyl)phosphonium HBF4 salt (4.6 mg, 0.016 mmol) were added to a vial, followed by dioxane (1.0 ml), DBU (0.095 ml, 0.63 mmol) and morpholine (0.027 ml, 0.32 mmol). The resulting suspension was purged with argon (subsurface bubbling) for 5 min. The reaction mixture was stirred at 100° C. for 16 hr in a sealed vial. The reaction mixture was diluted with ACN, MeOH, and DMSO and purified directly by preparative reverse phase HPLC, eluting with an acetonitrile/water (0.05% TFA modifier) gradient to afford 6-isopropyl-9-(morpholin-4-ylcarbonyl)benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO D-6) δ 11.86 (d, 1H), 10.07 (d, 1H), 8.53 (d, 1H), 7.74 (dd, 1H), 7.57 (t, 1H), 6.78 (dd, 1H), 4.10 (septet, 1H), 3.70 (br s, 4H), 3.55 (br s, 2H), 3.35 (br s, 2H), 1.38 (d, 6H). LRMS (ESI) calc'd for (C20H21N3O3) [M+H]+, 352.2; found 352.1.

Workup

  1. customThe resulting suspension was purged with argon (subsurface bubbling) for 5 min
  2. additionThe reaction mixture was diluted with ACN, MeOH, and DMSO
  3. custompurified directly by preparative reverse phase HPLC
  4. washeluting with an acetonitrile/water (0.05% TFA modifier) gradient

Sources & evidence

ORD record
ord-3b11ee0a621e4474b60761822b35c2a0
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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