Potassium Carbonate → HCID 11258090, compound

HRID 2354226Notes

Reaction equation

HRID 2354226 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:10][CH2:11][N:12](C(OC(C)(C)C)=O)[CH2:13][CH:14]=2)O1.C(=O)([O-])[O-].[K+].[K+].[CH:29]1([NH:32][C:33](=[O:53])[C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[C:36]([N:41]3[C:50](=[O:51])[C:49]4[C:44](=[CH:45][CH:46]=[C:47](I)[CH:48]=4)[N:43]=[CH:42]3)[CH:35]=2)[CH2:31][CH2:30]1>CN(C=O)C.C(OCC)(=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:29]1([NH:32][C:33](=[O:53])[C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[C:36]([N:41]3[C:50](=[O:51])[C:49]4[C:44](=[CH:45][CH:46]=[C:47]([C:9]5[CH2:10][CH2:11][NH:12][CH2:13][CH:14]=5)[CH:48]=4)[N:43]=[CH:42]3)[CH:35]=2)[CH2:31][CH2:30]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 11487616HCID 11487616, compound

Product 1

HCID 11258090HCID 11258090, compoundYield 43.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a nitrogen flushed flask containing tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (1.04 g), potassium carbonate (0.869 g), and 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride (0.11 g) was added a solution of N-cyclopropyl-3-(6-iodo-4-oxoquinazolin-3(4H)-yl)-4-methylbenzamide (1.0 g) in DMF (14 ml). The reaction mixture was stirred for 16 hours at 80° C. The reaction mixture was diluted with ethyl acetate and washed with water (5×), brine, dried (magnesium sulfate) and concentrated. The resulting solid was dissolved in 4N HCl in dioxane (5 ml) and methanol (5 ml) and stirred at room temperature for 2 hours. The precipitate was collected by filtration and washed with ethyl acetate and diethyl ether. Purification by column chromatography on a silica column eluting with 10% methanol/ethyl acetate followed by 20% methanol/ethyl acetate+1% aqueous ammonia solution gave N-cyclopropyl-4-methyl-3-[4-oxo-6-(1,2,3,6-tetrahydropyridin-4-yl)quinazolin-3(4H)-yl]benzamide (AZ12267331) (0.393 g) as a light brown solid; NMR Spectrum: (DMSOd6) 0.54 (m, 2H), 0.69 (m, 2H), 2.15 (s, 3H), 2.43 (m, 2H), 2.85 (m, 1H), 2.94 (t, 2H), 3.40 (s, 2H), 6.45 (s, 1H), 7.53 (d, 1H), 7.74 (d, 1H), 7.86 (s, 1H), 7.90 (d, 1H), 8.05 (d, 1H), 8.12 (s, 1H), 8.29 (s, 1H), 8.49 (d, 1H); Mass Spectrum: M+H+ 401.

Workup

  1. washwashed with water (5×), brine
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated
  4. dissolutionThe resulting solid was dissolved in 4N HCl in dioxane (5 ml)
  5. stirringmethanol (5 ml) and stirred at room temperature for 2 hours
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with ethyl acetate and diethyl ether
  8. customPurification by column chromatography on a silica column
  9. washeluting with 10% methanol/ethyl acetate

Sources & evidence

ORD record
ord-c6cd149354504db380e3354688c3da6c
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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