Cesium carbonate → 2-Furancarboxamide, N-[2-methyl-4-(1-pyrrolidinyl)-7-quinazolinyl]-

HRID 1271218Notes

Reaction equation

HRID 1271218 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:7][C:8]([CH3:12])=[N:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].N[C@@H]1CCCC[C@H]1N.[O:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[C:37]([NH2:39])=[O:38]>O1CCOCC1.[Cu]I>[CH3:12][C:8]1[N:7]=[C:6]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[C:5]2[C:10](=[CH:11][C:2]([NH:39][C:37]([C:33]3[O:32][CH:36]=[CH:35][CH:34]=3)=[O:38])=[CH:3][CH:4]=2)[N:9]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 69108FuramideHCID 224749397-Bromo-2-methyl-4-pyrrolidin-1-yl-quinazoline

Product 1

HCID 99734192-Furancarboxamide, N-[2-methyl-4-(1-pyrrolidinyl)-7-quinazolinyl]-Yield 22%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A suspension of 0.12 g (0.41 mmol) of 7-bromo-2-methyl-4-pyrrolidin-1-yl-quinazoline, 3.9 mg (0.021 mmol) of copper (I) iodide and 0.267 g (0.82 mmol) of caesium carbonate in dioxane (5 ml) was treated at RT under argon with 4.7 mg (0.041 mmol) of trans-1,2-diaminocyclohexane and 0.18 g (1.6 mmol) of 2-furamide and then heated at reflux under argon for 20 h. The reaction mixture was partitioned between EtOAc and water, the layers were separated, the organic layer washed twice with water dried over sodium sulphate and concentrated in vacuo. The residue was applied to silica gel column with CH2Cl2/MeOH/NH4OH (9:1:0.5) as eluent. Combination of the purified fractions and concentration in vacuo gave 29 mg (22%) of the furan-2-carboxylic acid (2-methyl-4-pyrrolidin-1-yl-quinazolin-7-yl)-amide as an off white solid. ISP mass spectrum, m/e: 323.4 (M+1 calculated for C18H18N4O2: 323).

Workup

  1. temperatureheated
  2. temperatureat reflux under argon for 20 h
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. customthe layers were separated
  5. washthe organic layer washed twice with water
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in vacuo
  8. concentrationCombination of the purified fractions and concentration in vacuo

Sources & evidence

ORD record
ord-daf25bfb61484ba7bd434f4615e8a6ba
Source dataset
uspto-grants-2007_04
Patent number
US07205309B2

Reaction notes

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