Hydrochloric Acid → HCID 66780337、化合物

HRID 1958033ノート

反応式

HRID 1958033 の反応式
[Cl:1][C:2]1[C:3]([CH3:24])=[C:4]([CH2:8][NH:9][C:10]2[N:11]=[C:12]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[S:13][C:14]=2[C:15]([NH2:17])=[O:16])[CH:5]=[CH:6][CH:7]=1.[C:25](OCC(Cl)=O)(=[O:27])[CH3:26].[OH-].[Na+].Cl>COCCOC.CO>[Cl:1][C:2]1[C:3]([CH3:24])=[C:4]([CH2:8][N:9]2[C:10]3[N:11]=[C:12]([N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[S:13][C:14]=3[C:15](=[O:16])[N:17]=[C:26]2[CH2:25][OH:27])[CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 26297Acetoxyacetyl chlorideHCID 66779830HCID 66779830、化合物

生成物 1

HCID 66780337HCID 66780337、化合物

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

To a solution of 4-{[(3-chloro-2-methylphenyl)methyl]amino}-2-(4-morpholinyl)-1,3-thiazole-5-carboxamide (1 g, 2.73 mmol) in 1,2-Dimethoxyethane (DME) (20 ml) at 0° C. was added acetoxyacetyl chloride (0.586 ml, 5.45 mmol). The mixture was stirred at room temperature for 2 h, then stirred at 50° C. overnight. The mixture was quenched with methanol and concentrated. To the resulting residue in Methanol (12 ml) was added 6N NaOH (0.9 mL, 5.45 mmol). The mixture was stirred at room temperature for 60 min, then acidified (˜pH 5) with 1N HCl. The solvent was removed and the residue was partitioned between dichloromethane and water. The organic layer was dried (sodium sulfate), filtered, and concentrated. Reversed-phase HPLC purification provided 4-[(3-chloro-2-methylphenyl)methyl]-5-(hydroxymethyl)-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one. (250 mg, 22%); LC/MS: MS (ES+) m/e 407 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3H), 3.51 (m, 4H), 3.67 (m, 4H), 4.32 (d, J=5.6 Hz, 2H), 5.57 (s, 2H), 5.64 (t, J=5.6 Hz, 1H, OH), 6.51 (d, J=7.6 Hz, 1H), 7.14 (m, 1H), 7.37 (d, J=7.8 Hz, 1H).

後処理

  1. stirringstirred at 50° C. overnight
  2. customThe mixture was quenched with methanol
  3. concentrationconcentrated
  4. stirringThe mixture was stirred at room temperature for 60 min
  5. customThe solvent was removed
  6. customthe residue was partitioned between dichloromethane and water
  7. dry with materialThe organic layer was dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customReversed-phase HPLC purification

出典と根拠

ORDレコード
ord-e2b343ee659748509db75ddabb059b25
出典データセット
uspto-grants-2013_04
特許番号
US08410095B2

反応ノート

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