Sodium Iodide → HCID 178493869, compound

HRID 536272Notes

Reaction equation

HRID 536272 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:7]([CH2:23][CH2:24][N:25]=3)[C:8]([NH:14][C:15]([C:17]3[CH:18]=[N:19][CH:20]=N[CH:22]=3)=[O:16])=[N:9][C:10]=2[C:11]=1[O:12][CH3:13].[C:26](=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].Br[CH2:35][CH2:36][CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42]>CN(C)C=O.O>[C:41]([O:40][C:39](=[O:45])[NH:38][CH2:37][CH2:36][CH2:35][O:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:7]([CH2:23][CH2:24][N:25]=3)[C:8]([NH:14][C:15]([C:17]3[CH:18]=[N:19][CH:20]=[CH:26][CH:22]=3)=[O:16])=[N:9][C:10]=2[C:11]=1[O:12][CH3:13])([CH3:44])([CH3:43])[CH3:42]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 178493833HCID 178493833, compound2×

Product 1

HCID 178493869HCID 178493869, compoundYield 51.9%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

N-(8-Hydroxy-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyrimidine-5-carboxamide (Intermediate B, 1.5 g, 4.4 mmol) was diluted in dimethylformamide (50 mL) containing a few drops of water. Cesium carbonate (7.24 g, 22.2 mmol) and sodium iodide (0.80 g, 5.3 mmol) were added, followed by tert-butyl (3-bromopropyl)carbamate (3.18 g, 13.3 mmol). The mixture was stirred at 100° C. overnight. After cooling to rt, the solvent was removed in vacuo. The residue was diluted in 10% methanol in dichloromethane, and solids were removed by filtration. The filtrate was concentrated and purified by silica gel flash column chromatography, eluting with 0-10% methanol in dichloromethane, to afford the title compound (1.13 g, 51%). 1H NMR (DMSO-d6+2 drops TFA-d) δ: 1.37 (9H, s), 1.94 (2H, m), 3.15 (2H, t), 4.03 (3H, s), 4.26 (4H, m), 4.57 (2H, m), 6.96 (1H, br t), 7.47 (1H, d), 7.82 (1H, m), 8.03 (1H, d), 8.79 (1H, m), 8.91 (1H, m), 9.46 (1H, m).

Workup

  1. temperatureAfter cooling to rt
  2. customthe solvent was removed in vacuo
  3. additionThe residue was diluted in 10% methanol in dichloromethane
  4. customsolids were removed by filtration
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel flash column chromatography
  7. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-420c4e81ab14402ca612dc231c458298
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

Loading…