2-Methyl-2-thiopseudourea → HCID 178473458, 화합물

HRID 12257

반응식

HRID 12257 반응식
CS[C:3](=[NH:5])[NH2:4].Cl[C:7]([O:9][CH2:10][CH3:11])=[O:8].[OH-].[Na+].N[C:15]1[C:20]([NH2:21])=[CH:19][C:18]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:17][C:16]=1[C:28](=[O:31])[CH2:29][CH3:30]>O.CCOC(C)=O.CC(O)=O>[CH2:10]([O:9][C:7](=[O:8])[NH:4][C:3]1[NH:5][C:15]2[C:16]([C:28](=[O:31])[CH2:29][CH3:30])=[CH:17][C:18]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)=[CH:19][C:20]=2[N:21]=1)[CH3:11]

참가 물질

8

반응물 4

HCID 51422-Methyl-2-thiopseudoureaHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 179849121-(2,3-Diamino-5-pyridin-3-yl-phenyl)-propan-1-one

생성물 1

HCID 178473458HCID 178473458, 화합물

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 962Water용매3회HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

To a mixture of 2-methyl-2-thiopseudourea (109 mg, 0.39 mmol) and ethyl chloroformate (75 μL, 0.78 mmol) in water (2 mL) at 5° C. was added over 40 minutes a 6N aqueous NaOH solution until pH stabilized to 8. The pH was then adjusted to 5 with glacial AcOH. A suspension of 1-(2,3-diamino-5-pyridin-3-yl-phenyl)-propan-1-one (0.30 mmol) in water (5 mL) was subsequently added to the reaction mixture. The reaction was heated at 90° C. for 18 hours, cooled to ambient temperature, and diluted with water (10 mL) and EtOAc (20 mL). The phases were separated and the aqueous layer extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried (MgSO4), filtered, and the filtrate concentrated in vacuo. The crude residue was taken up in DMSO, purified by preparative HPLC, and by flash column chromatography (SiO2; CH2Cl2:MeOH, 1:0 to 19:1). The residue was then converted to the bis-HCl salt to afford the title compound as an off white solid (5.0 mg): HPLC (10 to 90% CH3CN, 8 min.): Rt=3.90 minutes; 1H NMR (CD3OD, 500 MHz) δ 9.39 (d, 1H), 9.07 (d, 1H), 8.93 (d, 1H), 8.48 (d, 1H), 8.28 (d, 1H), 8.25 (dd, 1H), 4.46 (q, 2H), 3.35 (q, 2H), 1.43 (t, 3H), 1.29 (t, 3H); MS (ES+) m/z (M++1) 339.1.

후처리

  1. additionwas subsequently added to the reaction mixture
  2. temperaturecooled to ambient temperature
  3. customThe phases were separated
  4. extractionthe aqueous layer extracted with EtOAc (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo
  9. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-7c5490cbc6894f5eace522a61c214842
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727992B2

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