Potassium Carbonate → HCID 45257088, compound

HRID 422002Notes

Reaction equation

HRID 422002 reaction equation
Br.[NH2:2][C:3]1[N:4]=[C:5]([CH3:20])[C:6]2[CH:12]=[C:11](Br)[C:10](=[O:14])[N:9]([C@@H:15]3[CH2:19][CH2:18][O:17][CH2:16]3)[C:7]=2[N:8]=1.[NH2:21][C:22]1[CH:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][N:23]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:2][C:3]1[N:4]=[C:5]([CH3:20])[C:6]2[CH:12]=[C:11]([C:25]3[CH:24]=[N:23][C:22]([NH2:21])=[CH:27][CH:26]=3)[C:10](=[O:14])[N:9]([C@@H:15]3[CH2:19][CH2:18][O:17][CH2:16]3)[C:7]=2[N:8]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 66674223HCID 66674223, compound

Product 1

HCID 45257088HCID 45257088, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of (R)-2-amino-6-bromo-4-methyl-8-(tetrahydrofuran-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-one hydrobromide (2.97 g, 7.36 mmol) in 1,4-dioxane (100 mL) and water (25 mL) were added 2-aminopyridine-5-boronic acid pinacol ester (2.43 g, 11.0 mmol), K2CO3 (3.05 g, 22.1 mmol) and Pd(PPh3)4 (170 mg, 2 mol %) under a nitrogen atmosphere. The reaction mixture was heated at 95° C. for 3 h. After the reaction was complete by LC/MS, the reaction mixture was partitioned with ethyl acetate (200 mL). The precipitate in the aqueous layer was collected by filtration. Meanwhile, the aqueous layer was washed with ethyl acetate (100 mL×3) and the organic layers with brine. The organic layers were collected and dried with MgSO4, and the mixture filtered. The solvent was removed in vacuo to give a yellow solid. The combined solids were washed with ethyl acetate and water to give the desired product (1.96 g, 79% yield, >98% HPLC purity).

Workup

  1. customthe reaction mixture was partitioned with ethyl acetate (200 mL)
  2. filtrationThe precipitate in the aqueous layer was collected by filtration
  3. washMeanwhile, the aqueous layer was washed with ethyl acetate (100 mL×3)
  4. customThe organic layers were collected
  5. dry with materialdried with MgSO4
  6. filtrationthe mixture filtered
  7. customThe solvent was removed in vacuo
  8. customto give a yellow solid
  9. washThe combined solids were washed with ethyl acetate and water

Sources & evidence

ORD record
ord-02b05fb831514021ac5cfd88b8ca3ed6
Source dataset
uspto-grants-2012_01
Patent number
US08101622B2

Reaction notes

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