Hydrochloric Acid → HCID 66780015、化合物

HRID 1958030ノート

反応式

HRID 1958030 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([O:28][C@@H:29]([CH3:33])[C:30](Cl)=O)(=O)C.[OH-].[Na+].Cl>O1CCCC1.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:30]2[C@@H:29]([OH:28])[CH3:33])[CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 66779830HCID 66779830、化合物

生成物 1

HCID 66780015HCID 66780015、化合物

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran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 (200 mg, 0.545 mmol) in Tetrahydrofuran (THF) (20001) was added (1S)-2-chloro-1-methyl-2-oxoethyl acetate (164 mg, 1.090 mmol). The mixture was stirred at room temperature overnight, and then stirred at 60° C. for 3 h. To the mixture was added sodium hydroxide (454 μl, 2.73 mmol) and methanol (0.5 mL). After 30 min, the mixture was acidified (pH ˜5) with 6N HCl, and then concentrated. The residue was partitioned between dichloromethane and water. The organic layer was dried (sodium sulfate), filtered, and concentrated. The crude was purified by reversed-phase HPLC and subsequently converted to the HCl salt to provide 4-[(3-chloro-2-methylphenyl)methyl]-5-[(S)-1-hydroxyethyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one. (14 mg, 6%); LC/MS: MS (ES+) m/e 421 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (d, J=6.3 Hz, 3H), 2.44 (s, 3H), 3.53-3.62 (m, 4H), 3.67 (m, 4H), 4.57 (q, J=6.3 Hz, 1H), 5.67 (s, 2H), 6.51 (d, J=7.8 Hz, 1H), 7.14 (m, 1H), 7.37 (d, J=7.8 Hz, 1H).

後処理

  1. stirringstirred at 60° C. for 3 h
  2. waitAfter 30 min
  3. concentrationconcentrated
  4. customThe residue was partitioned between dichloromethane and water
  5. dry with materialThe organic layer was dried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by reversed-phase HPLC

出典と根拠

ORDレコード
ord-b38cef86171441979c029e15abdac854
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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