Formic Acid → 4-(Methylamino)quinazoline-2-thiol

HRID 44375Notes

Reaction equation

HRID 44375 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.NC(N)=[S:16].C(O)=O.[OH-].[Na+]>C(O)C>[CH3:13][NH:12][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3][C:2](=[S:16])[N:11]=1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 14798Sodium HydroxideHCID 3180572-chloro-N-methylquinazolin-4-amineHCID 2723790Thiourea

Product 1

HCID 25781794-(Methylamino)quinazoline-2-thiolYield 18.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-chloro-N-methylquinazolin-4-amine (Example 39) (100 mg, 0.52 mmol), thiourea (47.5 mg, 0.62 mmol) and formic acid (0.02 mL, 0.52 mmol) in ethanol (5 mL) was refluxed for 1.5 h. After cooling to room temperature, the reaction mixture was neutralized with diluted NaOH aqueous solution. The solvent was removed under vacuum and the residue was purified by preparative HPLC eluting with acetonitrile and water to give the title compound (18 mg, 18%). 1H NMR (400 MHz, DMSO-d6) δ2.99 (d, J=4.8 Hz, 3H), 7.25 (t, J=7.6 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.65-7.61 (m, 1H), 8.0 (d, J=8.0 Hz, 1H), 8.70 (d, J=4.4 Hz, 1H), 12.32 (s, 1H). MS 192 (MH+).

Workup

  1. temperaturewas refluxed for 1.5 h
  2. customThe solvent was removed under vacuum
  3. customthe residue was purified by preparative HPLC
  4. washeluting with acetonitrile and water

Sources & evidence

ORD record
ord-4dd6aaad7f17446eb3836b37f2167d3f
Source dataset
uspto-grants-2013_09
Patent number
US08541421B2

Reaction notes

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