Potassium Phosphate, Tribasic → HCID 86663958, compound

HRID 712164Notes

Reaction equation

HRID 712164 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH2:9]([NH:11][C:12]([NH:14][C:15]1[S:16][C:17]2[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[CH:22][C:21](C3C=NC(B(O)O)=NC=3)=[CH:20][C:18]=2[N:19]=1)=[O:13])[CH3:10].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:8][C:5]1[N:4]=[CH:3][C:2]([C:21]2[CH:22]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[C:17]3[S:16][C:15]([NH:14][C:12]([NH:11][CH2:9][CH3:10])=[O:13])=[N:19][C:18]=3[CH:20]=2)=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 6066655-Bromo-2-chloropyrimidineHCID 86663959HCID 86663959, compound

Product 1

HCID 86663958HCID 86663958, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromo-2-chloropyrimidine (6.80 g, 35.1 mmol) in DMF (40 mL) was added [5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]boronic acid (10 g, 29.24 mmol) and aqueous solution of K3PO4 (9.3 g, 43.86 mmol). The reaction mixture was degassed by purging N2 for 15 min followed by addition of bis(triphenylphosphine)palladium (II) chloride (3.10 g, 4.4 mmol). The reaction mixture was again degassed for 10-15 min then heated up to 80° C. for 2 h. After completion of reaction (by TLC), solvent was evaporated under reduced pressure, 50 mL water added followed by extraction with EtOAc (3×200 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 60-120 M silica-gel by using 5% MeOH: DCM to obtain an off white solid compound that was triturated with ether (4.80 g). Further product was obtained by repeating the extraction (1.20 g) giving a combined total product yield of 6.0 g (50%). 1H NMR (DMSO-d6): δ 1.12 (t, J=7.20 Hz, 3H), 3.20 (m, 2H), 6.83 (br s, 1H), 7.46 (m, 1H), 8.0 (m, 1H), 8.17 (s, 1H), 8.40 (s, 1H), 8.50 (d, J=8.0 Hz, 1H), 8.82 (d, J=4.0 Hz, 1H), 9.35 (s, 2H) and 10.61 (br s, 1H). MS: 411.16 [M+H]+.

Workup

  1. customThe reaction mixture was degassed
  2. customby purging N2 for 15 min
  3. customThe reaction mixture was again degassed for 10-15 min
  4. customAfter completion of reaction (by TLC), solvent
  5. customwas evaporated under reduced pressure, 50 mL water
  6. additionadded
  7. extractionfollowed by extraction with EtOAc (3×200 mL)
  8. washThe combined organics were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe crude residue was purified over 60-120 M silica-gel
  13. customDCM to obtain an off white solid compound that
  14. customwas triturated with ether (4.80 g)
  15. customFurther product was obtained
  16. extractionthe extraction (1.20 g)

Sources & evidence

ORD record
ord-4fa56b7f23cc4d959435f298e485ed45
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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