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

HRID 711644Notes

Reaction equation

HRID 711644 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) δ 2.99 (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-fad31ecd19df4d7ca887b66516f19e1f
Source dataset
uspto-grants-2015_11
Patent number
US09181276B2

Reaction notes

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