Cesium carbonate → HCID 59511795, compound

HRID 1157464Notes

Reaction equation

HRID 1157464 reaction equation
CS([O:5][C@H:6]1[CH2:10][CH2:9][C@@H:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:7]1)(=O)=O.[CH:17]1([CH2:20][NH:21][C:22](=[O:42])[CH2:23][N:24]2[C:33](=[O:34])[C:32]3[C:27](=[CH:28][CH:29]=[C:30](O)[CH:31]=3)[N:26]=[C:25]2[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:19][CH2:18]1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O>[CH:17]1([CH2:20][NH:21][C:22](=[O:42])[CH2:23][N:24]2[C:33](=[O:34])[C:32]3[C:27](=[CH:28][CH:29]=[C:30]([O:5][C@H:6]4[CH2:10][CH2:9][C@H:8]([N:11]5[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]5)[CH2:7]4)[CH:31]=3)[N:26]=[C:25]2[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:18][CH2:19]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 49866222HCID 49866222, compoundHCID 59511777HCID 59511777, compound

Product 1

HCID 59511795HCID 59511795, compoundYield 14.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of crude (1S,3R)-3-piperidin-1-ylcyclopentyl methanesulphonate (INTERMEDIATE XII.1) (90 mg, 0.4 mmol), N-cyclopropylmethyl-2-(6-hydroxy-4-oxo-2-phenyl-4H-quinazolin-3-yl)acetamide (INTERMEDIATE IV.6) (71 mg, 0.2 mmol) and Cs2CO3 (326 mg, 1.0 mmol) in DMSO (0.3 mL) was heated at 80° C. for 16 h. The mixture was then cooled and diluted with water. The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organics were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel with methanol:dichloromethane (1:9, v/v) as eluent to afford N-cyclopropylmethyl-2-[4-oxo-2-phenyl-6-((1S,3S)-3-piperidin-1-ylcyclopentyloxy)-4H-quinazolin-3-yl]acetamide (EXAMPLE 5a) (14 mg, 0.029 mmol, 14%).

Workup

  1. temperatureThe mixture was then cooled
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organics were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on silica gel with methanol:dichloromethane (1:9, v/v) as eluent

Sources & evidence

ORD record
ord-0b83122c1987433eb64a7f5e9f7dd455
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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