Cesium carbonate → 5-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine

HRID 1922764

Reaction equation

HRID 1922764 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.[CH2:17]([C:19]1[NH:20][C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=1)[CH3:18].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[CH2:17]([C:19]1[N:20]([C:2]2[N:3]=[C:4]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=2)[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=1)[CH3:18]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 576853854-(5-Chlorothiazolo[5,4-d]pyrimidin-7-yl)morpholine

Product 1

HCID 596056325-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine (3.0 g, 11.7 mmol), 2-ethylbenzimidazole (1.88 g, 12.9 mmol), tris(dibenzylideneacetone)dipalladium (534 mg, 0.60 mmol), XPhos (1.11 g, 2.34 mmol) and Cs2CO3 (7.62 g, 23 4 mmol) in dioxane (60 mL) was purged with argon then heated at 120° C. for 16 h in a sealed tube. The reaction mixture was filtered through Celite®, and the filtrated partitioned between EtOAc and H2O. The organic phase was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:DCM, 0-90%) followed by recrystallisation from iPrOAc affording the title compound (3.17 g, 74%). LCMS (method A): RT 2.74 min [M+H]+ 367.1

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through Celite®
  3. customthe filtrated partitioned between EtOAc and H2O
  4. washThe organic phase was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:DCM, 0-90%)
  8. customfollowed by recrystallisation from iPrOAc affording the title compound (3.17 g, 74%)
  9. customRT 2.74 min [M+H]+ 367.1

Sources & evidence

ORD record
ord-fd29f7bce32b42da9ab4fcda52cd0e0d
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Linked notes

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