Cesium carbonate → HCID 59392827, compound

HRID 216737Notes

Reaction equation

HRID 216737 reaction equation
Cl[CH2:2][CH2:3][O:4]C.[F:6][C:7]1[CH:8]=[C:9]([C:21]2[CH:22]=[CH:23][CH:24]=[C:25]3[C:30]=2[N:29]=[C:28]([C:31]2[CH:32]=[N:33][N:34]([CH:36]4[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]4)[CH:35]=2)[CH:27]=[N:26]3)[CH:10]=[C:11]([F:20])[C:12]=1[CH2:13][N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[F:6][C:7]1[CH:8]=[C:9]([C:21]2[CH:22]=[CH:23][CH:24]=[C:25]3[C:30]=2[N:29]=[C:28]([C:31]2[CH:32]=[N:33][N:34]([CH:36]4[CH2:41][CH2:40][N:39]([C:3](=[O:4])[CH3:2])[CH2:38][CH2:37]4)[CH:35]=2)[CH:27]=[N:26]3)[CH:10]=[C:11]([F:20])[C:12]=1[CH2:13][N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 123162-Chloroethyl methyl etherHCID 46398810HCID 46398810, compound

Product 1

HCID 59392827HCID 59392827, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

2-chloroethylmethyl ether (13.5 μl, 0.143 mmol) is added dropwise to a solution of 8-(3,5-Difluoro-4-morpholin-4-ylmethyl-phenyl)-2-(1-piperidin-4-yl-1H-pyrazol-4-yl)-quinoxaline (as obtained in example 98, 67 mg, 0.137 mmol), Cs2CO3 (24 mg, 0.075 mmol) in DMF (0.5 ml). The resulting mixture is heated under Ar at 95° C. for 17 h. Two products are formed in a ratio 1:1, as identified by example 122 and example 123. The reaction is quenched with water and extracted with EtOAc several times. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2/(CH2Cl2:EtOH:NH3 90:9:1) from 1:0=>0:1) to afford example 122 and example 123.

Workup

  1. customTwo products are formed in a ratio 1:1
  2. customThe reaction is quenched with water
  3. extractionextracted with EtOAc several times
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated in vacuo
  8. customThe residue is purified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2/(CH2Cl2:EtOH:NH3 90:9:1) from 1:0=>0:1)
  9. customto afford example 122 and example 123

Sources & evidence

ORD record
ord-77a017534792436899578a7f009ba931
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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