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

HRID 1922768Notes

Reaction equation

HRID 1922768 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[N:10]=[C:9]([CH:11]=[O:12])[S:8][C:6]=2[N:7]=1.[CH2:19]([C:21]1[NH:22][C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[N:25]=1)[CH3:20].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]>[CH2:19]([C:21]1[N:22]([C:2]2[N:3]=[C:4]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:5]3[N:10]=[C:9]([CH:11]=[O:12])[S:8][C:6]=3[N:7]=2)[C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[N:25]=1)[CH3:20]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 576854055-Chloro-7-morpholinothiazolo[5,4-d]pyrimidine-2-carbaldehyde

Product 1

HCID 596058695-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine-2-carbaldehydeYield 88.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
115 °C

Procedure

A mixture of 5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine-2-carbaldehyde (1.0 g, 3.51 mmol), 2-ethylbenzimidazole (512 mg, 3.71 mmol), tris(dibenzylideneacetone)dipalladium (90 mg, 2.5 mol %), XPhos (158 mg, 10 mol %) and Cs2CO3 (1.6 g, 4.91 mmol) in dioxane (30 mL) was purged with argon then heated at 115° C. for 17 h. The reaction mixture was filtered through Celite® which was washed with hot dioxane, and the filtrated concentrated in vacuo. The resulting residue was triturated with Et2O and the resulting brown solid collected by filtration and dried in vacuo affording the title compound (1.23 g, 88%). 1H NMR (CDCl3, 400 MHz): δ 10.01 (1 H, s), 8.09-8.09 (1 H, m), 7.75-7.74 (1 H, m), 7.33-7.26 (2 H, m), 5.00-4.00 (4 H, brd s), 3.93 (4 H, t, J=4.72 Hz), 3.37 (2 H, q, J=7.45 Hz), 1.46 (3 H, t, J=7.45 Hz).

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through Celite® which
  3. washwas washed with hot dioxane
  4. concentrationthe filtrated concentrated in vacuo
  5. customThe resulting residue was triturated with Et2O
  6. filtrationthe resulting brown solid collected by filtration
  7. customdried in vacuo

Sources & evidence

ORD record
ord-5887f53c4f844b159c8077d814717bef
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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