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

HRID 12257

Reaction equation

HRID 12257 reaction equation
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]

Participants

8

Reactant 4

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

Product 1

HCID 178473458HCID 178473458, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-7c5490cbc6894f5eace522a61c214842
Source dataset
uspto-grants-2010_06
Patent number
US07727992B2

Linked notes

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