Acetyl chloride → HCID 68510566, compound

HRID 1712004Notes

Reaction equation

HRID 1712004 reaction equation
C(N(CC)CC)C.[C:8](Cl)(=[O:10])[CH3:9].Cl.Cl.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:34][CH3:35])=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[C:24]([N:36]3[CH2:41][CH2:40][CH:39]([N:42]([CH3:50])[C:43](=[O:49])[C@@H:44]4[CH2:48][CH2:47][CH2:46][NH:45]4)[CH2:38][CH2:37]3)[N:23]=2)=[C:17]([F:51])[CH:16]=1.C(=O)(O)[O-].[Na+]>ClCCl>[C:8]([N:45]1[CH2:46][CH2:47][CH2:48][C@H:44]1[C:43]([N:42]([CH:39]1[CH2:38][CH2:37][N:36]([C:24]2[N:23]=[C:22]([NH:21][C:18]3[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][C:17]=3[F:51])[C:31]3[C:26](=[CH:27][C:28]([O:34][CH3:35])=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=2)[CH2:41][CH2:40]1)[CH3:50])=[O:49])(=[O:10])[CH3:9]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 68506459HCID 68506459, compound

Product 1

HCID 68510566HCID 68510566, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (175 μl) and acetyl chloride (32 μl) were added under ice-cooling to a dichloromethane (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 under ice-cooling for 2 hours and under room temperature for 20 hours. A saturated sodium bicarbonate aqueous solution was added thereto, 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), 1-acetyl-N-(1-{4-[(4-chloro-2-fluorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)-N-methyl-L-prolinamide was obtained. This compound was dissolved in MeOH (3 mL), 4 M HCl/ethyl acetate solution (203 μl) was added thereto, and the solvent was evaporated. By crystallizing the resulting crude crystals from isopropanol-diisopropyl ether, 1-acetyl-N-(1-{4-[(4-chloro-2-fluorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}piperidin-4-yl)-N-methyl-L-prolinamide hydrochloride (167 mg) was obtained as pale yellow crystals.

Workup

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

Sources & evidence

ORD record
ord-fc1ca6ba71c344d09b793e9a508630be
Source dataset
uspto-grants-2010_09
Patent number
US07790884B2

Reaction notes

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