Potassium Hydroxide → Afatinib

HRID 2423012Notes

Reaction equation

HRID 2423012 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:32][C@H:33]4[CH2:37][CH2:36][O:35][CH2:34]4)=[C:17]([NH:20][C:21]([CH2:23]P(=O)(OCC)OCC)=[O:22])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[Cl-].[Li+].[OH-].[K+].[CH3:42][N:43]([CH2:45][CH:46]=O)[CH3:44].S([O-])(O)=O>C(O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:32][C@H:33]4[CH2:37][CH2:36][O:35][CH2:34]4)=[C:17]([NH:20][C:21](=[O:22])/[CH:23]=[CH:46]/[CH2:45][N:43]([CH3:44])[CH3:42])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 433294Lithium ChlorideHCID 15606393Diethyl (2-{[4-(3-chloro-4-fluoroanilino)-7-{[(3S)-oxolan-3-yl]oxy}quinazolin-6-yl]amino}-2-oxoethyl)phosphonateHCID 86636908HCID 86636908, compound

Product 1

HCID 10184653Afatinib

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
-5 °C

Procedure

10 g of diethyl {[4-(3-chloro-4-fluoro-phenylamino)-7-((S)-tetrahydrofuran-3-yloxy)-quinazolin-6-ylcarbamoyl]-methyl}-phosphonate and 0.8 g lithium chloride are suspended in 60 ml of ethanol and cooled to −5° C. 11 g of 45% potassium hydroxide solution is added dropwise first of all and then 4.8 g dimethylaminoacetaldehyde-hydrogen sulphite adduct in 48 ml of water is added. The reaction solution is stirred for 1 h and then 60 ml of water are added. The suspension is suction filtered, washed with 40 ml of water and dried in vacuo at 45° C.

Workup

  1. additionis added
  2. filtrationsuction filtered
  3. washwashed with 40 ml of water
  4. customdried in vacuo at 45° C.

Sources & evidence

ORD record
ord-08d631c37dfc4fae82a11e9e5b25eb2c
Source dataset
uspto-grants-2011_06
Patent number
US07960546B2

Reaction notes

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