Methyl iodide → Methyl-(2-methyl-4,5-dihydro-thiazolo[4,5-h]quinazolin-8-yl)-(3-nitro-phenyl)-amine

HRID 2102791Notes

Reaction equation

HRID 2102791 reaction equation
[CH3:1][C:2]1[S:3][C:4]2[C:13]3[N:12]=[C:11]([NH:14][C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=4)[N:10]=[CH:9][C:8]=3[CH2:7][CH2:6][C:5]=2[N:24]=1.[H-].[Na+].I[CH3:28]>CN(C=O)C>[CH3:28][N:14]([C:11]1[N:10]=[CH:9][C:8]2[CH2:7][CH2:6][C:5]3[N:24]=[C:2]([CH3:1])[S:3][C:4]=3[C:13]=2[N:12]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 11163580HCID 11163580, compound

Product 1

HCID 11451037Methyl-(2-methyl-4,5-dihydro-thiazolo[4,5-h]quinazolin-8-yl)-(3-nitro-phenyl)-amineYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2-methyl-4,5-dihydro-thiazolo[4,5-h]quinazolin-8-yl)-(3-nitro-phenyl)-amine (100 mg, 0.3 mmol) in dry DMF (2 mL) was added NaH (7.8 mg, 0.3 mmol) under anhydrous conditions. Once H2 evolution had ceased, iodomethane (22 μL, 50 mg, 0.4 mmol) was added dropwise and the mixture was stirred at room temperature overnight. It was then concentrated under vacuum and H2O (20 mL) was added. The product was extracted with CH2Cl2 (3×30 mL). The combined extracts were dried, filtered, and concentrated under vacuum. Flash column chromatography (10% EtOAc:hexane) afforded the pure title product as a yellow solid (40 mg, 38%): mp 203-204° C. Anal. RP-HPLC: tR 17.1 min (10-70% MeCN, purity 85%). 1H-NMR (CDCl3): δ 8.30 (t, 1H, J 2.3, Ph-H), 8.11 (s, 1H, Py-H), 7.95 (ddd, 1H, J 8.2, 2.3, 1.0, Ph-H), 7.65 (ddd, 1H, J 8.2, 2.3, 1.0, Ph-H), 7.44 (t, 1H, J 8.2, Ph-H), 3.58 (s, 3H, N—CH3), 2.98 (m, 4H, CH2—CH2), 2.69 (s, 3H, CH3). 13C-NMR (CDCl3): δ 169.86, 160.70, 159.30, 157.05, 155.27, 148.71, 146.74, 131.42, 129.33, 120.81, 119.36, 116.63, 38.18, 25.68, 24.22, 20.17. MS (ESI+): m/z 354.09 (M+H)+.

Workup

  1. concentrationIt was then concentrated under vacuum and H2O (20 mL)
  2. additionwas added
  3. extractionThe product was extracted with CH2Cl2 (3×30 mL)
  4. customThe combined extracts were dried
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-999e70c945184b3db283fcee6c48fd2c
Source dataset
uspto-grants-2009_08
Patent number
US07576091B2

Reaction notes

Loading…