Potassium Carbonate → HCID 73438321, compound

HRID 2203260Notes

Reaction equation

HRID 2203260 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[C:12](=[O:27])[NH:13][C:14](=[O:26])[N:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=4)[C:5]=3[C:4]=2[N:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[N:38][C:39]([NH2:42])=[N:40][CH:41]=2)O1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>Cl.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.O>[NH2:42][C:39]1[N:40]=[CH:41][C:36]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[C:12](=[O:27])[NH:13][C:14](=[O:26])[N:15]([C:16]5[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=5)[C:5]=4[C:4]=3[N:3]=2)=[CH:37][N:38]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 90077584HCID 90077584, compound

Product 1

HCID 73438321HCID 73438321, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

9-chloro-1-(3-(trifluoromethyl)phenyl)pyrimidino[5,4-c][1,5]naphthyridine-2,4(1H,3H)-dione (300 mg, 0.77 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (170 mg, 0.77 mmol), potassium carbonate (317 mg, 2.3 mmol) and tetrakis(triphenylphosphine)palladium (45 mg, 0.04 mmol) were added to 40 mL dioxane and 2 mL water. The resulting mixture was reacted under reflux in the nitrogen protection for 18 hrs, cooled to room temperature, and concentrated. 400 mL water was added. The resulting mixture was filtered to obtain a crude product, which was dissolved in 20 mL 6M concentrated hydrochloric acid, and washed with dichloromethane (4×50 mL). The aqueous phase was added dropwise to an aqueous sodium carbonate solution, filtered, and washed with water. The resulting crude product was washed with methanol to produce 9-(2-aminopyrimidin-5-yl)-1-(3-(trifluoromethyl)phenyl)pyrimidino[5,4-c][1,5]naphthyridine-2,4(1H,3H)-dione (160 mg).

Workup

  1. customThe resulting mixture was reacted
  2. temperatureunder reflux in the nitrogen protection for 18 hrs
  3. concentrationconcentrated
  4. addition400 mL water was added
  5. filtrationThe resulting mixture was filtered
  6. customto obtain a crude product, which
  7. washwashed with dichloromethane (4×50 mL)
  8. additionThe aqueous phase was added dropwise to an aqueous sodium carbonate solution
  9. filtrationfiltered
  10. washwashed with water
  11. washThe resulting crude product was washed with methanol

Sources & evidence

ORD record
ord-a48f151ca8384246903979d4721bc096
Source dataset
uspto-grants-2016_06
Patent number
US09365572B2

Reaction notes

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