2-Fluoro-4-nitroaniline → 3-Benzyl-5-((2-fluoro-4-nitrophenyl)amino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 2067735Notes

Reaction equation

HRID 2067735 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15](Cl)=[CH:16][C:17](=[O:20])[N:18]([CH3:19])[C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:22][C:23]1[CH:29]=[C:28]([N+:30]([O-:32])=[O:31])[CH:27]=[CH:26][C:24]=1[NH2:25].CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15]([NH:25][C:24]3[CH:26]=[CH:27][C:28]([N+:30]([O-:32])=[O:31])=[CH:29][C:23]=3[F:22])=[CH:16][C:17](=[O:20])[N:18]([CH3:19])[C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 1012542-Fluoro-4-nitroanilineHCID 23676156Sodium t-butoxideHCID 598230573-Benzyl-5-chloro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Product 1

HCID 598230443-Benzyl-5-((2-fluoro-4-nitrophenyl)amino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dioneYield 69%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Benzyl-5-chloro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (950 mg, 3.15 mmol, 1 eq), 2-fluoro-4-nitroaniline (540 mg, 3.46 mmol, 1.1 eq), tris(dibenzylideneacetone)dipalladium(0) (58 mg, 0.06 mmol, 0.02 eq), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (36 mg, 0.06 mmol, 0.02 eq) and sodium tert-butoxide (453 mg, 4.7 mmol, 1.5 eq) were mixed in degassed anhydrous dioxane (7 mL) and subjected to microwave irradiation at 100° C. for 30 minutes. Upon cooling a precipitate formed which was filtered and washed with cold dioxane (3 mL) to give 910 mg of the title compound (69%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.55 (s, 3 H) 5.23 (s, 2 H) 6.14 (s, 1 H) 7.29-7.41 (m, 5 H) 7.81-7.94 (m, 1 H) 8.14 (d, J=10.86 Hz, 1 H) 8.25 (d, J=11.12 Hz, 1 H) 8.96 (s, 1 H) 11.23 (s, 1 H) [M+H] calc'd for C21H16FN5O4, 422; found, 422.

Workup

  1. customirradiation at 100° C. for 30 minutes
  2. temperatureUpon cooling a precipitate
  3. customformed which
  4. filtrationwas filtered
  5. washwashed with cold dioxane (3 mL)

Sources & evidence

ORD record
ord-95dafd0d977246ba944ec690a4d14f3e
Source dataset
uspto-grants-2012_10
Patent number
US08293901B2

Reaction notes

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