Hydrochloric Acid → HCID 66780015, 화합물

HRID 1958030노트

반응식

HRID 1958030 반응식
[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

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 66779830HCID 66779830, 화합물

생성물 1

HCID 66780015HCID 66780015, 화합물

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b38cef86171441979c029e15abdac854
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410095B2

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