Potassium Phosphate, Tribasic → 4-(4-(5-(Methylthio)imidazo[1,2-c]pyrimidin-7-yl)phenyl)morpholine

HRID 1853041Notes

Reaction equation

HRID 1853041 reaction equation
Cl.Cl[C:3]1[N:8]=[C:7]([S:9][CH3:10])[N:6]2[CH:11]=[CH:12][N:13]=[C:5]2[CH:4]=1.[O:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=2)[CH2:16][CH2:15]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C(O)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:10][S:9][C:7]1[N:6]2[CH:11]=[CH:12][N:13]=[C:5]2[CH:4]=[C:3]([C:23]2[CH:22]=[CH:21][C:20]([N:17]3[CH2:16][CH2:15][O:14][CH2:19][CH2:18]3)=[CH:25][CH:24]=2)[N:8]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2795359(4-(Morpholin-4-yl)phenyl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866852967-Chloro-5-(methylthio)imidazo[1,2-c]pyrimidine hydrochloride

Product 1

HCID 674576914-(4-(5-(Methylthio)imidazo[1,2-c]pyrimidin-7-yl)phenyl)morpholineYield 25.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 7-chloro-5-(methylthio)imidazo[1,2-c]pyrimidine hydrochloride (1.85 g, 7.83 mmol; Preparation H, Step A), 4-morpholinophenylboronic acid (1.78 g, 8.62 mmol) and potassium phosphate (3.33 g, 15.7 mmol) in isopropanol (25 mL) was purged with argon for 5 minutes, and then Pd2dba3 (0.717 g, 0.783 mmol) and XPHOS (1.49 g, 3.13 mmol) were added. The reaction was again purged for 5 minutes with argon before being sealed and heated to 90° C. for 18 hours. The reaction mixture was diluted with EtOAc (75 mL) and filtered. The filtrate was concentrated under reduced pressure, and the residue obtained was purified by silica gel column chromatography, eluting with 10-15-20% acetone in DCM to afford 4-(4-(5-(methylthio)imidazo[1,2-c]pyrimidin-7-yl)phenyl)morpholine (0.663 g, 25.9% yield) as a yellow solid. MS (apci) m/z=327.1 (M+H).

Workup

  1. customwas purged with argon for 5 minutes
  2. customThe reaction was again purged for 5 minutes with argon
  3. custombefore being sealed
  4. additionThe reaction mixture was diluted with EtOAc (75 mL)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue obtained
  8. customwas purified by silica gel column chromatography
  9. washeluting with 10-15-20% acetone in DCM

Sources & evidence

ORD record
ord-8950542511ea4a74b1e3e701b44305a4
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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