Isopropanol → Erlotinib Hydrochloride

HRID 1016387Notes

Reaction equation

HRID 1016387 reaction equation
[ClH:1].[CH3:2][O:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[O:17][CH2:18][CH2:19][O:20][CH3:21])[N:13]=[CH:12][N:11]=[C:10]2[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[C:30][Si](C)(C)C)[CH:24]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CC(O)C>O1CCCC1>[ClH:1].[C:29]([C:25]1[CH:24]=[C:23]([NH:22][C:10]2[C:9]3[C:14](=[CH:15][C:16]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:7]([O:6][CH2:5][CH2:4][O:3][CH3:2])[CH:8]=3)[N:13]=[CH:12][N:11]=2)[CH:28]=[CH:27][CH:26]=1)#[CH:30]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 2724141Tetrabutylammonium FluorideHCID 9957698HCID 9957698, compound

Product 1

HCID 176871Erlotinib HydrochlorideYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A slurry of the silyl compound, 6,7-bis(2-methoxyethoxy)-N-[3-[(trimethylsilyl)ethynyl]phenyl]-4-quinazolinamine monohydrochloride, prepared above (1.22 g, 2.43 mmol) in tetrahydrofuran (6.1 mL) was treated with a 1M solution of tetra-n-butylammonium fluoride in tetrahydrofuran (2.6 mL, 2.55 mmol) and stirred at room temperature for 1 hour. The solution was treated with 2-propanol (12.2 mL) and concentrated by evaporation. The oil in 2-propanol (20 mL) was treated with concentrated hydrochloric acid (0.2 mL) giving a precipitate. The mixture was stirred at room temperature for 1 hour. The solid was collected by filtration, washed with 2-propanol (2 mL) and dried in vacuo to afford the title product (747 mg, 72%) as an off white solid (mp 226-229° C.).

Workup

  1. concentrationconcentrated by evaporation
  2. additionThe oil in 2-propanol (20 mL) was treated with concentrated hydrochloric acid (0.2 mL)
  3. customgiving a precipitate
  4. stirringThe mixture was stirred at room temperature for 1 hour
  5. filtrationThe solid was collected by filtration
  6. washwashed with 2-propanol (2 mL)
  7. customdried in vacuo

Sources & evidence

ORD record
ord-a48217b1353343549ce000196ffae992
Source dataset
uspto-grants-2002_11
Patent number
US06476040B1

Reaction notes

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