Potassium Carbonate → N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(pyrrolidin-1-yl)ethoxy]quinazolin-4-amine

HRID 547168

Reaction equation

HRID 547168 reaction equation
Cl.N1CCCC1.[Cl:7][C:8]1[CH:27]=[CH:26][C:11]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([OH:25])=[C:20]([O:23][CH3:24])[CH:21]=3)[N:16]=[CH:15][N:14]=2)=[C:10]([F:28])[CH:9]=1.C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:37][CH2:38][N:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1>CN(C=O)C>[Cl:7][C:8]1[CH:27]=[CH:26][C:11]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:25][CH2:37][CH2:38][N:39]4[CH2:43][CH2:42][CH2:41][CH2:40]4)=[C:20]([O:23][CH3:24])[CH:21]=3)[N:16]=[CH:15][N:14]=2)=[C:10]([F:28])[CH:9]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 212848Pyrrolidine, hydrochloride (1:1)HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 5329018N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(pyrrolidin-1-yl)ethoxy]quinazolin-4-amineYield 10%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

1-2-Chloroethyl)pyrrolidine hydrochloride (200 mg, 1.2 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (403 mg, 1.26 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (650 mg, 4.7 mmol) in DMF (4 ml). The mixture was heated to 100° C. and further portions of 1-(2-chloroethyl)pyrrolidine hydrochloride (800 mg in total) were added periodically over 4 hours while the reaction mixture was maintained at 100° C. The reaction was then allowed to cool and volatiles were removed by evaporation. The residue was partitioned between methylene chloride and water, separated and the organic phase passed through phase separating paper. Column chromatography eluting with methylene chloride/methanol (95/5) gave 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline (50 mg, 10%).

Workup

  1. custom(prepared
  2. temperaturewas maintained at 100° C
  3. temperatureto cool
  4. customvolatiles were removed by evaporation
  5. customThe residue was partitioned between methylene chloride and water
  6. customseparated
  7. customseparating paper
  8. washColumn chromatography eluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record
ord-2494c1ce89174d669c97ecc127d586c6
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Linked notes

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