Hydrochloric Acid → HCID 66780490、化合物

HRID 1958031ノート

反応式

HRID 1958031 の反応式
[CH3:1][O:2][CH2:3][CH2:4][C:5](Cl)=O.[Cl:8][C:9]1[C:10]([CH3:31])=[C:11]([CH2:15][NH:16][C:17]2[N:18]=[C:19]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[S:20][C:21]=2[C:22]([NH2:24])=[O:23])[CH:12]=[CH:13][CH:14]=1.[OH-].[Na+].Cl>COCCOC>[Cl:8][C:9]1[C:10]([CH3:31])=[C:11]([CH2:15][N:16]2[C:17]3[N:18]=[C:19]([N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[S:20][C:21]=3[C:22](=[O:23])[N:24]=[C:5]2[CH2:4][CH2:3][O:2][CH3:1])[CH:12]=[CH:13][CH:14]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27597283-Methoxypropanoyl chlorideHCID 66779830HCID 66779830、化合物

生成物 1

HCID 66780490HCID 66780490、化合物

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒2 回

実験手順

3-methoxypropionyl chloride (66.8 mg, 0.545 mmol) in 1,2-Dimethoxyethane (DME) (400 μl) was added to a solution of 4-{[(3-chloro-2-methylphenyl)methyl]amino}-2-(4-morpholinyl)-1,3-thiazole-5-carboxamide (100 mg, 0.273 mmol) in 1,2-Dimethoxyethane (DME) (1000 μl). The mixture was stirred at room temperature overnight, then quenched with methanol and concentrated. To the residue was added methanol (1 mL) followed by 6N NaOH (1 equiv.). The mixture was stirred at room temperature for 3 h, neutralized (pH ˜8) with 6N HCl, and concentrated. The residue was partitioned between dichloromethane and water. The organic layer was dried (sodium sulfate), filtered, and concentrated. The crude product was purified by reversed-phase HPLC and the fractions were neutralized with sat. aq. sodium bicarbonate. The combined fractions were concentrated to remove acetonitrile and the remaining water was extracted with dichloromethane. The organic layer was dried (sodium sulfate), filtered, and concentrated to provide 4-[(3-chloro-2-methylphenyl)methyl]-5-[2-(methyloxy)ethyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one. (14 mg, 12%); LC/MS: MS (ES+) m/e 435 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.44 (s, 3H), 2.80 (t, J=6.7 Hz, 2H), 3.19 (s, 3H), 3.52 (m, 4H), 3.62-3.72 (m, 6H), 5.57 (s, 2H), 6.51 (d, J=7.6 Hz, 1H), 7.16 (m, 1H), 7.39 (d, J=7.8 Hz, 1H).

後処理

  1. customquenched with methanol
  2. concentrationconcentrated
  3. additionTo the residue was added methanol (1 mL)
  4. stirringThe mixture was stirred at room temperature for 3 h
  5. concentrationconcentrated
  6. customThe residue was partitioned between dichloromethane and water
  7. dry with materialThe organic layer was dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by reversed-phase HPLC
  11. concentrationThe combined fractions were concentrated
  12. customto remove acetonitrile
  13. extractionthe remaining water was extracted with dichloromethane
  14. dry with materialThe organic layer was dried (sodium sulfate)
  15. filtrationfiltered
  16. concentrationconcentrated

出典と根拠

ORDレコード
ord-092effa2ac11489e91db36813fc4f18b
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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