Sodium Carbonate → HCID 54741096, compound

HRID 420446Notes

Reaction equation

HRID 420446 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[CH:10][C:11]3[C:17]([OH:18])=[C:16]([C:19]([NH:21][CH2:22][C:23]([O:25]C(C)(C)C)=[O:24])=[O:20])[C:15](=[O:30])[N:14]([CH3:31])[C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1.ClC1N=CC2C(O)=C(C(NCC(OC(C)(C)C)=O)=O)C(=O)N(C)C=2N=1.FC1C=C(B(O)O)C=CC=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[CH:10][C:11]3[C:17]([OH:18])=[C:16]([C:19]([NH:21][CH2:22][C:23]([OH:25])=[O:24])=[O:20])[C:15](=[O:30])[N:14]([CH3:31])[C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 57657530HCID 57657530, compoundHCID 86629413HCID 86629413, compound

Product 1

HCID 54741096HCID 54741096, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 2-(2-(3-fluorophenyl)-5-hydroxy-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamido)acetate. To a mixture of tert-butyl 2-(2-chloro-5-hydroxy-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamido)acetate (100 mg, 1 eq., Method 10), Pd(dppf)Cl2 (0.05 eq.), 3-fluorophenylboronic acid (3.0 eq., available from Aldrich (Milwaukee, Wis.)) in degassed dioxane (4 mL) was added degassed aqueous Na2CO3 (2M, 3 eq.) in a sealed tube. The mixture was stirred overnight at 80° C. The mixture was then cooled to room temperature and diluted with water. The phases were separated and extracted with more CH2Cl2. The combined organic phases were washed with water and brine, dried over Na2SO4 and concentrated. The residue was dissolved in DMA and purified on reversed phase HPLC to give the title compound (48 mg, 41%) as a light brown solid. C21H21FN4O5 (428.4). APCI-MS: 429 ([M+H]+), 373 ([M-(t-Bu)+H]+). 1H-NMR (DMSO-d6): δ 10.21 (br s, 1H), 9.39 (s, 1H), 8.40 (d, J=7.8, 1H), 8.25 (d, J=9.3, 1H), 7.66 (q, J=8.1, 1H), 7.49 (dt, J=8.5, 2.5, 1H), 4.13 (d, J=5.7, 2H), 3.55 (s, 3H), 1.46 (s, 9H).

Workup

  1. additionwas added
  2. temperatureThe mixture was then cooled to room temperature
  3. customThe phases were separated
  4. extractionextracted with more CH2Cl2
  5. washThe combined organic phases were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in DMA
  9. custompurified on reversed phase HPLC

Sources & evidence

ORD record
ord-d11076b1529042d6ba70926f9c3c9c99
Source dataset
uspto-grants-2012_01
Patent number
US08097620B2

Reaction notes

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