Cesium carbonate → Methyl 3-amino-6-{[2-(4-chlorophenyl)-1,3-oxazol-4-yl]methoxy}-5-cyano-4-[4-(2-hydroxyethoxy)phenyl]-1-methyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

HRID 1913508Notes

Reaction equation

HRID 1913508 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH:10]=[C:11]([CH2:13][O:14][C:15]3[N:20]=[C:19]([N:21]([CH3:27])[CH2:22][C:23]([O:25][CH3:26])=[O:24])[C:18]([C:28]#[N:29])=[C:17]([C:30]4[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][OH:39])=[CH:32][CH:31]=4)[C:16]=3[C:40]#[N:41])[N:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[NH2:29][C:28]1[C:18]2[C:19](=[N:20][C:15]([O:14][CH2:13][C:11]3[N:12]=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[O:9][CH:10]=3)=[C:16]([C:40]#[N:41])[C:17]=2[C:30]2[CH:31]=[CH:32][C:33]([O:36][CH2:37][CH2:38][OH:39])=[CH:34][CH:35]=2)[N:21]([CH3:27])[C:22]=1[C:23]([O:25][CH3:26])=[O:24]

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 66672288Methyl N-(6-{[2-(4-chlorophenyl)-1,3-oxazol-4-yl]methoxy}-3,5-dicyano-4-[4-(2-hydroxyethoxy)phenyl]pyridin-2-yl)-N-methylglycinate

Product 1

HCID 44124048Methyl 3-amino-6-{[2-(4-chlorophenyl)-1,3-oxazol-4-yl]methoxy}-5-cyano-4-[4-(2-hydroxyethoxy)phenyl]-1-methyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

20 mg (0.04 mmol) of the compound from Example 51A were initially charged in 1 ml of acetonitrile, and 45 mg (0.14 mmol) of cesium carbonate were added. The reaction mixture was stirred at 50° C. for 4 h. After cooling to RT, the mixture was filtered off. The precipitate was washed with acetonitrile and suspended in water. The mixture was extracted three times with in each case 10 ml of ethyl acetate, and the combined organic phases were dried over magnesium sulfate. After removal of the solvent on a rotary evaporator, the residue was purified directly by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5). Removal of the solvent on a rotary evaporator gave the product as a solid.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe mixture was filtered off
  3. washThe precipitate was washed with acetonitrile
  4. extractionThe mixture was extracted three times with in each case 10 ml of ethyl acetate
  5. dry with materialthe combined organic phases were dried over magnesium sulfate
  6. customAfter removal of the solvent
  7. customon a rotary evaporator
  8. customthe residue was purified directly by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)
  9. customRemoval of the solvent
  10. customon a rotary evaporator

Sources & evidence

ORD record
ord-2364d637509a4267bf2394060e63142b
Source dataset
uspto-grants-2013_12
Patent number
US08609686B2

Reaction notes

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