Dichloromethane → N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl) propoxy)quinazolin-4-amine

HRID 712440Notes

Reaction equation

HRID 712440 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:21][CH3:22])=[C:17]([OH:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([O-])([O-])=O.[K+].[K+].Cl[CH2:30][CH2:31][CH2:32][N:33]1[CH2:37][CH:36]2[CH2:38][O:39][CH2:40][CH:35]2[CH2:34]1.C(Cl)Cl>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([O:20][CH2:30][CH2:31][CH2:32][N:33]4[CH2:37][CH:36]5[CH2:38][O:39][CH2:40][CH:35]5[CH2:34]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 867294855-(3-chloropropyl)hexahydro-1H-furo[3,4-c]pyrrole

Product 1

HCID 71573377N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(tetrahydro-1H-furo[3,4-c]pyrrol-5(3H)-yl) propoxy)quinazolin-4-amineYield 64%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.19 g) in DMF (6 mL) was added K2CO3 (0.42 g) and tetrabutylammonium iodide (20 mg). The mixture was stirred at room temperature for 10 min, to this, a solution of 5-(3-chloropropyl)hexahydro-1H-furo[3,4-c]pyrrole (0.13 g) in DMF (2 mL) was added. The reaction mixture was heated at 80° C. for 14 h under N2 and treated with CH2Cl2 (100 mL), then washed with water and brine. The mixture was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound (180 mg, 60.04%), HPLC: 95.78%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 474.0 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.12 (t, J=13.28 Hz, 2H), 2.54 (s, 2H), 2.72 (t, J=13.32 Hz, 2H), 2.83 (d, J=9.00 Hz, 2H), 2.90 (s, 2H), 3.73 (t, J=5.36 Hz, 3H), 3.99 (s, 3H), 4.28 (t, J=13.24 Hz, 2H), 7.15 (t, J=17.60 Hz, 1H), 7.25 (d, J=7.32 Hz, 1H), 7.44 (s, 1H), 7.60-7.64 (m, 1H), 7.93-7.96 (m, 1H), 7.99 (s, 1H), 8.64 (s, 1H) ppm.

Workup

  1. temperatureThe reaction mixture was heated at 80° C. for 14 h under N2
  2. washwashed with water and brine
  3. dry with materialThe mixture was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-83de88d33aab402f969eaa1a34f00948
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

Loading…