Potassium Carbonate → HCID 58495646, compound

HRID 1191105Notes

Reaction equation

HRID 1191105 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)[N:3]=1.[C:13]([O:17][C:18]([NH:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>C1(C)C=CC=CC=1.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.C(O)C>[CH:10]1([CH2:9][NH:8][C:4]2[N:3]=[C:2]([C:25]3[CH:26]=[CH:27][C:22]([CH2:21][NH:20][C:18]([O:17][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:19])=[CH:23][CH:24]=3)[CH:7]=[CH:6][N:5]=2)[CH2:12][CH2:11]1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 38631634-(tert-Butoxycarbonylaminomethyl)phenylboronic acidHCID 58495643HCID 58495643, compound

Product 1

HCID 58495646HCID 58495646, compoundYield 91%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

Slurry 4-chloro-2-(cyclopropylmethyl-amino)-pyrimidine (155 mg, 0.62 mmol), [4-(N-tert-butoxycarbonyl-aminomethyl)phenyl]boronic acid (160 mg, 0.86 mmol), and tetrakis(triphenylphosphine)palladium(0) (36 mg, 0.031 mmol) in toluene (3 mL). Add ethanol (0.5 mL) followed by potassium carbonate (175 mg, 1.24 mmol) dissolved in water (300 μL). Irradiate in microwave (300 watts) at 120° C. for 60 min. Cool to room temperature, pour reaction mixture into water (100 mL) containing 1N NaOH (25 mL) and extract with DCM (3×50 mL). Wash the combined organic extracts with brine, dry over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (12 g) eluting with hexane/EtOAc (4:1 to 3:7 over 30 min; 30 mL/min) to obtain the desired intermediate (200 mg, 90%) as a light yellow solid. MS (ES+) m/z: 355 (M+H)+.

Workup

  1. customIrradiate in microwave (300 watts) at 120° C. for 60 min
  2. additionpour
  3. extractionextract with DCM (3×50 mL)
  4. washWash the combined organic extracts with brine
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel (12 g)
  9. washeluting with hexane/EtOAc (4:1 to 3:7 over 30 min; 30 mL/min)

Sources & evidence

ORD record
ord-28a9ded540df4debaa2219fdb67597c6
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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