Dimethyl Sulfoxide → HCID 59375669, compound

HRID 2192989Notes

Reaction equation

HRID 2192989 reaction equation
[Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9](I)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.[C:25]([NH:28][NH2:29])(=[O:27])[CH3:26].[C:30](P)([CH3:33])([CH3:32])[CH3:31].[H+].[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.CS(C)=[O:52]>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]>[Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9]([C:25]([NH2:28])=[O:27])=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.[C:25]([NH:28][NH:29][C:31]([C:30]1[C:33]2[N:7]=[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[C:5]3[CH:23]=[CH:24][C:2]([Br:1])=[CH:3][C:4]=3[C:13]=2[C:12](=[O:14])[NH:11][CH:32]=1)=[O:52])(=[O:27])[CH3:26]

Participants

8

Reactant 5

HCID 679Dimethyl SulfoxideHCID 14039AcetohydrazideHCID 81531DiisopropylethylamineHCID 59375664HCID 59375664, compoundHCID 131730108HCID 131730108, compound

Product 2

HCID 59375669HCID 59375669, compoundHCID 59375678HCID 59375678, compound

Reagents, catalysts & solvents 1

HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Conditions

Temperature
100 °C

Procedure

9-bromo-4-iodo-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one (100 mg, 0.20 mmol), acetic hydrazide (16.3 mg, 0.220 mmol), Mo(CO)6 (52.8 mg, 0.200 mmol), t-butylphosphine HBF4 salt (5.80 mg, 0.020 mmol), and trans-di-mu-acetatobis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) (9.38 mg, 10.00 mmol) were added to a microwave vial and flushed with nitrogen. Dioxane (2000 μl) was added followed by Hunig's base (34.9 μl 0.200 mmol) and degassed for 10 min with subsurface N2 bubbling. The reaction flask was then sealed and heated to 100° C. for 2 h. The crude reaction mixture was then diluted with DMSO and purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA, to give the title compound as a white solid and also N′-acetyl-9-bromo-1-oxo-6-[(1,2,2-trimethylpropyl)amino]-1,2-dihydrobenzo[c]-1,6-naphthyridine-4-carbohydrazide as a white solid. 1H NMR (500 MHz, CD3OD) δ 11.88 (d, 1H, J=6.0 Hz), 10.14 (d, 1H, J=2.0 Hz), 10.03 (d, 1H, J=4.0 Hz), 8.56 (d, 1H, J=9.0 Hz), 8.20 (d, 1H, J=7.0 Hz), 7.85 (m, 3H), 4.21 (m, 1H), 1.22 (d, 3H, J=13.5 Hz), 0.96 (s, 9H). LRMS (ESI) calc'd for (C19H22BrN4O2) [M+H]+, 417.1; found 417.0.

Workup

  1. customflushed with nitrogen
  2. additionDioxane (2000 μl) was added
  3. customdegassed for 10 min with subsurface N2 bubbling
  4. customThe reaction flask was then sealed
  5. customThe crude reaction mixture
  6. custompurified by preparative HPLC Reverse phase (C-18)
  7. washeluting with Acetonitrile/Water+0.05% TFA

Sources & evidence

ORD record
ord-d0045f90889e41b98fab9a5fd2f956be
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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