Hydrochloric Acid → 2-Furancarboxaldehyde,5-[4-[[3-chloro-4-[(3-fluorophenyl)Methoxy]phenyl]aMino]-6-quinazolinyl]-, Mono(4-Methylbenzenesulfonate)

HRID 724250

Reaction equation

HRID 724250 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([CH:24]=[CH:25][C:26]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[O:21][C:20]([CH:22]=[O:23])=[CH:19][CH:18]=3)[CH:15]=2)[N:10]=[CH:9][N:8]=1.ClC1C=C(NC2C3C(=CC=C(C4OC(CNCC[S:72](C)(=[O:74])=[O:73])=CC=4)C=3)N=CN=2)C=CC=1OCC1C=CC=C(F)C=1.[OH-:76].[Na+]>C1COCC1>[S:72]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)([OH:74])(=[O:76])=[O:73].[Cl:2][C:3]1[CH:4]=[C:5]([CH:24]=[CH:25][C:26]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[O:21][C:20]([CH:22]=[O:23])=[CH:19][CH:18]=3)[CH:15]=2)[N:10]=[CH:9][N:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 208908LapatinibHCID 11181296(5-(4-(4-((3-Fluorobenzyl)oxy)-3-chloroanilino)-6-quinazolinyl)-2-furancarboxaldehyde

Product 1

HCID 111812952-Furancarboxaldehyde,5-[4-[[3-chloro-4-[(3-fluorophenyl)Methoxy]phenyl]aMino]-6-quinazolinyl]-, Mono(4-Methylbenzenesulfonate)

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 2 liter, 3 neck round bottom flask equipped with a mechanical stirrer was charged with 74.95 grams of the HCl salt of 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde (prepared according to the Procedure D and Examples 1 (a)–(g), and 749.5 mL THF. To this slurry was charged 84.45 mL of 2M NaOH and the reactants were stirred for 30 minutes. The layers were separated and then the organic layer was washed with 160 mL of H2O. The organic layer was slurried with 3.75 grams of Darco G60 and filtered through celite. The filtrate was collected and slowly added to 33.54 grams of toluenesulfonic acid monohydrate with rapid stirring. The solids slowly precipitated out at ambient temperature. The mixture was cooled to 0° C. and stirred for 10 minutes. The mixture was filtered and pulled dry with a rubber dam, then dried in vacuo at 50° C. overnight. The yield of 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde tosylate was 84.25 grams (88.8%).

Workup

  1. customA 2 liter, 3 neck round bottom flask equipped with a mechanical stirrer
  2. customprepared
  3. customThe layers were separated
  4. washthe organic layer was washed with 160 mL of H2O
  5. filtrationand filtered through celite
  6. customThe filtrate was collected
  7. additionslowly added to 33.54 grams of toluenesulfonic acid monohydrate with rapid stirring
  8. customThe solids slowly precipitated out at ambient temperature
  9. stirringstirred for 10 minutes
  10. filtrationThe mixture was filtered
  11. custompulled dry with a rubber dam
  12. customdried in vacuo at 50° C. overnight

Sources & evidence

ORD record
ord-b5c62d26aa7a4f79888ea4bd97ae9d20
Source dataset
uspto-grants-2006_11
Patent number
US07141576B2

Linked notes

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