Potassium Carbonate → tert-Butyl 5-amino-2-methylthio-4-(3-(2-(pyrrolidin-1-yl)-ethoxy)-phenyl)-quinazoline-6-carboxamide

HRID 1766087Notes

Reaction equation

HRID 1766087 reaction equation
C([O-])([O-])=O.[K+].[K+].Cl.Cl[CH2:9][CH2:10][N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1.[C:16]([C:20]1[CH:29]=[C:28]2[C:23]([C:24]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([OH:38])[CH:33]=3)=[N:25][C:26]([S:30][CH3:31])=[N:27]2)=[C:22]([NH2:39])[C:21]=1[C:40]([NH2:42])=[O:41])([CH3:19])([CH3:18])[CH3:17]>CC(C)=O>[C:16]([C:20]1[CH:29]=[C:28]2[C:23]([C:24]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH2:9][CH2:10][N:11]4[CH2:15][CH2:14][CH2:13][CH2:12]4)[CH:33]=3)=[N:25][C:26]([S:30][CH3:31])=[N:27]2)=[C:22]([NH2:39])[C:21]=1[C:40]([NH2:42])=[O:41])([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 21109116tert-Butyl 5-amino-2-methylthio-4-(3-hydroxyphenyl)-quinazoline-6-carboxamide

Product 1

HCID 21109110tert-Butyl 5-amino-2-methylthio-4-(3-(2-(pyrrolidin-1-yl)-ethoxy)-phenyl)-quinazoline-6-carboxamide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of K2CO3 (1.0 g), 1-(2-chloroethyl)pyrrolidine hydrochloride (66 mg) and tert-butyl 5-amino-2-methylthio-4-(3-hydroxyphenyl)-quinazoline-6-carboxamide (example 26a, 121 mg) in acetone was heated overnight at reflux. The mixture was cooled to room temperature, the solids were removed by filtration and the filtrate concentrated under reduced pressure. The residue was taken up in EtOAc and washed with water and brine. The organic phase was dried (MgSO4) and concentrated in vacuo. The title compound was purified by HPLC using a Luna C-18 column with the following gradient: 10% aq. CH3CN/CH3CN/0.1% aq. TFA=72/25/3 to 27/70/3 (v/v/v) in 30 min. The title compound was lyophilized from a nixture of water, TFA is and CH3CN.

Workup

  1. temperaturewas heated overnight
  2. temperatureat reflux
  3. customthe solids were removed by filtration
  4. concentrationthe filtrate concentrated under reduced pressure
  5. washwashed with water and brine
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe title compound was purified by HPLC

Sources & evidence

ORD record
ord-85f7e2ba71c345e9b66af5ae84d69418
Source dataset
uspto-grants-2007_06
Patent number
US07229990B2

Reaction notes

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