Sodium Iodide → 2-[2-(3-chloro-4-fluorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide

HRID 1157459Notes

Reaction equation

HRID 1157459 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:18]([CH2:19][C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])[C:17](=[O:26])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:27][CH2:28][CH2:29][CH2:30]Cl)[CH:15]=3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([O-])([O-])=O.[K+].[K+].[NH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1.[I-].[Na+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:18]([CH2:19][C:20]([NH:22][CH:23]([CH3:24])[CH3:25])=[O:21])[C:17](=[O:26])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:27][CH2:28][CH2:29][CH2:30][N:38]4[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]4)[CH:15]=3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8082PiperidineHCID 11430Potassium CarbonateHCID 595117802-[2-(3-chloro-4-fluorophenyl)-6-(3-chloropropoxy)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide

Product 1

HCID 118545042-[2-(3-chloro-4-fluorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamideYield 91%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 2-[2-(3-chloro-4-fluorophenyl)-6-(3-chloropropoxy)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide (120 mg, 0.26 mmol) in acetonitrile (1 mL) was added K2CO3 (178 mg, 1.29 mmol), piperidine (0.76 mL, 0.77 mmol) and sodium iodide (20 mg, 0.13 mmol). The resultant mixture was heated to 80° C. in a tightly capped vial with stirring for 20 h. The mixture was then cooled to room temperature and poured into ice water (8 mL). The resultant white solid was collected by filtration and the filter cake was washed with cold diethyl ether (3×10 mL). The crude product was purified by chromatography on silica gel with methanol:dichloromethane (1:9, v/v) as eluent to afford 2-[2-(3-chloro-4-fluorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide (120 mg, 0.23 mmol, 91%). The HCl salt was prepared by treating the freebase with 5% HCl in ethanol (xs.) followed by removal of the ethanolic HCl in vacuo. The resultant HCl salt was redissolved in ethanol and the ethanol removed in vacuo (3×) to help remove residual HCl. The HCl salt thus obtained was then triturated with diethyl ether and collected by filtration affording 2-[2-(3-chloro-4-fluorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide hydrochloride (EXAMPLE 2a) as a white crystalline solid.

Workup

  1. filtrationThe resultant white solid was collected by filtration
  2. washthe filter cake was washed with cold diethyl ether (3×10 mL)
  3. customThe crude product was purified by chromatography on silica gel with methanol:dichloromethane (1:9, v/v) as eluent

Sources & evidence

ORD record
ord-edbf97c0ed6d4455a5e7987402f595f9
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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