2-Fluoro-4-iodoaniline → (R)-3-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 2090560Notes

Reaction equation

HRID 2090560 reaction equation
Cl[C:2]1[C:11]2[C:10](=[O:12])[N:9]([CH2:13][C@@H:14]3[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[O:15]3)[CH:8]=[N:7][C:6]=2[N:5]([CH3:21])[C:4](=[O:22])[C:3]=1[F:23].[F:24][C:25]1[CH:31]=[C:30]([I:32])[CH:29]=[CH:28][C:26]=1[NH2:27].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:19][C:16]1([CH3:20])[O:15][C@H:14]([CH2:13][N:9]2[C:10](=[O:12])[C:11]3[C:2]([NH:27][C:26]4[CH:28]=[CH:29][C:30]([I:32])=[CH:31][C:25]=4[F:24])=[C:3]([F:23])[C:4](=[O:22])[N:5]([CH3:21])[C:6]=3[N:7]=[CH:8]2)[CH2:18][O:17]1

Participants

8

Reactant 4

HCID 1856942-Fluoro-4-iodoanilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 67378564(R)-5-Chloro-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Product 1

HCID 67368877(R)-3-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Combine (R)-5-chloro-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (0.050 g, 0.15 mmol) and 2-fluoro-4-iodoaniline (0.052 g, 0.22 mmol) in de-gassed dioxane (2.0 mL). Add palladium acetate (1.6 mg) and Xantphos (8.5 mg) and sodium t-butoxide (35 mg). Heat to 85° C. After 2 hours, dilute with ethyl acetate, wash with aqueous hydrochloric acid and then brine, dry over sodium sulfate, and concentrate in vacuo to give a residue. Purify the residue with flash chromatography eluting with ethyl acetate/hexane to give the title compound.

Workup

  1. washwash with aqueous hydrochloric acid
  2. dry with materialbrine, dry over sodium sulfate
  3. concentrationconcentrate in vacuo
  4. customto give a residue
  5. customPurify the residue with flash chromatography
  6. washeluting with ethyl acetate/hexane

Sources & evidence

ORD record
ord-e2ac9528cdef4bd599465c4cebd2a10f
Source dataset
uspto-grants-2013_05
Patent number
US08436200B2

Reaction notes

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