Iodoethane → HCID 68501649, compound

HRID 1712005Notes

Reaction equation

HRID 1712005 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH2:7](I)[CH3:8].Cl.Cl.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:32][CH3:33])=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[C:22]([N:34]3[CH2:39][CH2:38][CH:37]([N:40]([CH3:48])[C:41](=[O:47])[C@@H:42]4[CH2:46][CH2:45][CH2:44][NH:43]4)[CH2:36][CH2:35]3)[N:21]=2)=[C:15]([F:49])[CH:14]=1>C(#N)C>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:32][CH3:33])=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[C:22]([N:34]3[CH2:35][CH2:36][CH:37]([N:40]([CH3:48])[C:41](=[O:47])[C@@H:42]4[CH2:46][CH2:45][CH2:44][N:43]4[CH2:7][CH3:8])[CH2:38][CH2:39]3)[N:21]=2)=[C:15]([F:49])[CH:14]=1

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 68506459HCID 68506459, compound

Product 1

HCID 68501649HCID 68501649, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

Potassium carbonate (62 mg) and ethyl iodide (36 μl) were added in that order to an acetonitrile (5 mL) solution of N-(1-{4-[(4-chloro-2-fluorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)-N-methyl-L-prolinamide dihydrochloride (250 mg), followed by stirring at room temperature for 2 hours and at 50° C. for 19 hours. The solvent was evaporated, and a saturated sodium bicarbonate aqueous solution was added to the resulting residue, followed by extraction with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. Then, the solvent was evaporated. By purifying the resulting residue by a silica gel column chromatography (chloroform-MeOH), N-(1-{4-[(4-chloro-2-fluorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)-1-ethyl-N-methyl-L-prolinamide was obtained. This compound was dissolved in MeOH (3 mL), 4 M HCl/ethyl acetate solution (198 μl) was added thereto, and the solvent was evaporated. By recrystallizing the resulting crude crystals from isopropanol-diisopropyl ether, N-(1-{4-[(4-chloro-2-fluorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)-1-ethyl-N-methyl-L-prolinamide dihydrochloride (101 mg) was obtained as pale yellow crystals.

Workup

  1. customThe solvent was evaporated
  2. additiona saturated sodium bicarbonate aqueous solution was added to the resulting residue
  3. extractionfollowed by extraction with chloroform
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThen, the solvent was evaporated
  7. customBy purifying the resulting residue by a silica gel column chromatography (chloroform-MeOH)

Sources & evidence

ORD record
ord-910228ce31f2433e9e65c9bd4df77cef
Source dataset
uspto-grants-2010_09
Patent number
US07790884B2

Reaction notes

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