1,2-Dichloroethane → 3-(3-Chlorophenyl)-7-trifluoromehyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide

HRID 229448Notes

Reaction equation

HRID 229448 reaction equation
[OH-].[Na+].C(O[C:6]([C:8]1[C:9]([C:24]([F:27])([F:26])[F:25])=[N:10][C:11]2[N:12]([C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=3)=[CH:15][N:16]=2)[CH:13]=1)=[O:7])C.C(Cl)CCl.C1[CH:33]=[CH:34][C:35]2N(O)N=[N:38][C:36]=2C=1.[O:42]1CCC[CH2:44][CH:43]1CN.C(N(CC)CC)C>C1COCC1.CO>[O:42]1[CH2:33][CH2:34][CH:35]([CH2:36][NH:38][C:6]([C:8]2[C:9]([C:24]([F:27])([F:26])[F:25])=[N:10][C:11]3[N:12]([C:14]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=4)=[CH:15][N:16]=3)[CH:13]=2)=[O:7])[CH2:44][CH2:43]1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 97924(Tetrahydro-2H-pyran-2-ylmethyl)amineHCID 577584783-(3-Chlorophenyl)-7-trifluoromehyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester

Product 1

HCID 250051893-(3-Chlorophenyl)-7-trifluoromehyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amideYield 43%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydroxide solution (2N, 0.4 mL) was added to 3-(3-chlorophenyl)-7-trifluoromehyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester (137 mg, 0.370 mmol) in THF (1.6 mL) and methanol (0.4 mL) at room temperature. The resulting solution was stirred for 2 hours then concentrated to dryness. Ethyl acetate was added and removed in vacuo three times. The crude residue was diluted in DMF (1.5 mL) and EDC (3 eq, 1.11 mmol, 213 mg), HOBt (3 eq, 1.11 mmol, 150 mg) were added. The mixture was stirred for 15 minutes, then tetrahydropyran-methylamine (1.5 eq, 64 mg) and triethyl amine (3 eq, 1.11 mmol, 0.16 mL) were added. The resulting mixture was stirred overnight. The reaction mixture was quenched by the addition of aqueous NH4Cl solution and the product was extracted with ethyl acetate. The crude product was purified using column chromatography (using 2% methanol/EtOAc as eluent) to afford 3-(3-chlorophenyl)-7-trifluoromehyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide in 43% yield. 1H NMR (DMSO-d6) δ 11.65 (1H), 8.50-8.52 (2H), 8.19 (1H), 8.01 (1H), 7.48 (1H), 7.41 (1H), 3.92 (2H), 372 (2H), 3.31 (2H), 1.92 (1H), 1.58 (2H), 1.31 (2H); m/z (M+H)=439.3.

Workup

  1. concentrationthen concentrated to dryness
  2. additionEthyl acetate was added
  3. customremoved in vacuo three times
  4. additionThe crude residue was diluted in DMF (1.5 mL)
  5. stirringThe mixture was stirred for 15 minutes
  6. stirringThe resulting mixture was stirred overnight
  7. customThe reaction mixture was quenched by the addition of aqueous NH4Cl solution
  8. extractionthe product was extracted with ethyl acetate
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-e54e67c050b94f4fb2863103de507ee3
Source dataset
uspto-grants-2009_07
Patent number
US07563797B2

Reaction notes

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