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

HRID 229448ノート

反応式

HRID 229448 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e54e67c050b94f4fb2863103de507ee3
出典データセット
uspto-grants-2009_07
特許番号
US07563797B2

反応ノート

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