Oxalyl chloride → N-benzyl-N-cyclobutyl-4-(2-fluorophenyl)-2-morpholinopyrimidine-5-carboxamide

HRID 1036616Notes

Reaction equation

HRID 1036616 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[C:19]([C:20](O)=[O:21])=[CH:18][N:17]=[C:16]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:15]=1.[CH2:29]([NH:36][CH:37]1[CH2:40][CH2:39][CH2:38]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C=O)C>[CH2:29]([N:36]([CH:37]1[CH2:38][CH2:39][CH2:40]1)[C:20]([C:19]1[C:14]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[F:7])=[N:15][C:16]([N:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)=[N:17][CH:18]=1)=[O:21])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 15365280N-BenzylcyclobutanamineHCID 217124094-(2-Fluorophenyl)-2-morpholinopyrimidine-5-carboxylic acid

Product 1

HCID 59421294N-benzyl-N-cyclobutyl-4-(2-fluorophenyl)-2-morpholinopyrimidine-5-carboxamideYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2M oxalyl chloride in CH2Cl2 (0.062 mL, 0.125 mmol) was added to a stirred solution of 4-(2-fluorophenyl)-2-morpholinopyrimidine-5-carboxylic acid (Example 1; 0.03 g, 0.1 mmol) in CH2Cl2(2 mL) and DMF (0.030 mL) at room temperature, and stirring continued for 15 min. A solution of N-benzylcyclobutanamine (0.016 g, 0.1 mmol) in CH2Cl2(1 mL) and diisopropylethylamine (0.044 mL, 0.25 mmol) were added and stirred for 3 h. 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-benzyl-N-cyclobutyl-4-(2-fluorophenyl)-2-morpholinopyrimidine-5-carboxamide (0.032 g, 72%). Mass Spec. FIA MS 447 (M+1), 1H NMR (DMSO-d6, 500 MHz) δ 8.43 (brs, 1H), 7.52-7.55 (m, 2H), 6.99-7.31 (m, 7H), 4.62 (brm, 2H), 3.78 (brm, 4H0, 3.68 (brm, 4H), 2.15 (brm, 2H), 1.85 (brm, 2H), 1.17 (brm, 2H).

Workup

  1. stirringstirred for 3 h
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was purified by Biotage SP1

Sources & evidence

ORD record
ord-65d5450d567c4163987e10df5fbfc132
Source dataset
uspto-grants-2013_10
Patent number
US08546414B2

Reaction notes

Loading…