Hydrochloric Acid → Erlotinib Hydrochloride

HRID 523966Notes

Reaction equation

HRID 523966 reaction equation
C(O)CCCC.[C:7]([C:9]1[CH:10]=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:31][CH2:32][CH2:33][O:34][CH3:35])=[C:23]([O:26][CH2:27][CH2:28][O:29][CH3:30])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1)#[CH:8].[ClH:36]>Cl.C(O)CCCC>[CH3:30][O:29][CH2:28][CH2:27][O:26][C:23]1[CH:24]=[C:25]2[C:16]([NH:15][C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([C:7]#[CH:8])[CH:10]=3)=[N:17][CH:18]=[N:19][C:20]2=[CH:21][C:22]=1[O:31][CH2:32][CH2:33][O:34][CH3:35].[ClH:36]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 62761-Pentanol2×HCID 176870Erlotinib

Product 1

HCID 176871Erlotinib HydrochlorideYield 91.5%

Reagents, catalysts & solvents 1

HCID 86692115HCID 86692115, compoundSolvent

Conditions

Temperature
22.5 °C

Procedure

In a 2.0 liter, 4 neck, round bottom flask equipped with a mechanical stirrer, a thermometer pocket and a reflux condenser, 420 ml of 1-pentanol (16.8 volumes with respect to erlotinib base) and 25 g (0.0635 mol) of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine (erlotinib base) was charged at 25-30° C. under stirring. The reaction mixture was then cooled to 20-25° C. to obtain a suspension. 30 ml of 1-pentanol-HCl solution (prepared by scrubbing HCl gas into 1-pentanol to a concentration by assay of 16-18% (w/w)) was added drop wise over a period of 15 minutes at a temperature of 20-25° C. The reaction mixture was stirred for a further 1 hour. The product was isolated by filtration, washed with 25 ml of 1-pentanol, and dried under reduced pressure (50 mm Hg) at 50-55° C., to give 25 g of erlotinib hydrochloride polymorph A (loss on drying <0.5%).

Workup

  1. customIn a 2.0 liter, 4 neck, round bottom flask equipped with a mechanical stirrer
  2. customto obtain a suspension
  3. concentrationto a concentration by assay of 16-18% (w/w))
  4. additionwas added drop wise over a period of 15 minutes at a temperature of 20-25° C
  5. stirringThe reaction mixture was stirred for a further 1 hour
  6. customThe product was isolated by filtration
  7. washwashed with 25 ml of 1-pentanol
  8. customdried under reduced pressure (50 mm Hg) at 50-55° C.

Sources & evidence

ORD record
ord-20c646d7e1494df4a23f47ffe67db76b
Source dataset
uspto-grants-2016_05
Patent number
US09340515B2

Reaction notes

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