Sodium Hydroxide → HCID 59421144, compound

HRID 1036617Notes

Reaction equation

HRID 1036617 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([C:14]([O:16]CC)=O)=[CH:12][N:11]=[C:10]([S:19][CH3:20])[N:9]=1.[OH-].[Na+].C(Cl)(=O)C(Cl)=O.[CH3:29][O:30][C:31]1[CH:32]=[C:33]([CH:39]=[CH:40][CH:41]=1)[CH2:34][NH:35][CH:36]([CH3:38])[CH3:37].C(N(C(C)C)CC)(C)C>C(O)C.O.C(Cl)Cl.CN(C=O)C>[CH3:29][O:30][C:31]1[CH:32]=[C:33]([CH:39]=[CH:40][CH:41]=1)[CH2:34][N:35]([CH:36]([CH3:38])[CH3:37])[C:14]([C:13]1[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[N:9][C:10]([S:19][CH3:20])=[N:11][CH:12]=1)=[O:16]

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 17156044N-[(3-Methoxyphenyl)methyl]propan-2-amineHCID 59421256Ethyl 4-(2-fluorophenyl)-2-(methylthio)-5-pyrimidinecarboxylate

Product 1

HCID 59421144HCID 59421144, compoundYield 23.5%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A mixture of ethyl 4-(2-fluorophenyl)-2-(methylthio)pyrimidine-5-carboxylate (3.3 g, 10.96 mmol), solid NaOH (3.2 g) in ethanol (30 mL) and water (6 mL) was refluxed for 1 h. and cooled to room temperature. The solvent was removed under reduced pressure, and the residue was acidified with 6N HCl. The product was extracted with EtOAC (3×50 mL), and the organic extracts were dried and concentrated to give crude acids (1.6 g). A solution of 2 M oxalyl chloride in CH2Cl2 (3.00 mL, 6 mmol) was added to a stirred solution of the crude acids (1.6 g) in CH2Cl2 (25 mL) and DMF (1 mL) at room temperature, and stirring continued for 15 min. A solution of N-(3-methoxybenzyl)propan-2-amine, (1.07 g, 6.00 mmol) in CH2Cl2(2 mL) and diisopropylethylamine (2 mL, 12 mmol) was added and stirred for 1 hr. The solvent was removed under reduced pressure and the residue was purified by Biotage SP1 on packed silica gel column (10%-80% EtOAc/Hexanes gradient) to give N-(3-methoxybenzyl)-4-(2-fluorophenyl)-N-isopropyl-2(methylthio)pyrimidine-5-carboxamide (0.6 g, 13%). Mass Spec. FIA MS 426 (M+1).

Workup

  1. temperaturewas refluxed for 1 h.
  2. customThe solvent was removed under reduced pressure
  3. extractionThe product was extracted with EtOAC (3×50 mL)
  4. customthe organic extracts were dried
  5. concentrationconcentrated
  6. customto give crude acids (1.6 g)
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by Biotage SP1

Sources & evidence

ORD record
ord-f164aa392fee4d14887e7721a897f474
Source dataset
uspto-grants-2013_10
Patent number
US08546414B2

Reaction notes

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