Dichloromethane → HCID 71573378, compound

HRID 712445Notes

Reaction equation

HRID 712445 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][CH2:39][O:40][CH2:41][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][CH2:39][O:40][CH2:41][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 86729488HCID 86729488, compound

Product 1

HCID 71573378HCID 71573378, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (60 mg) in DMF (6 mL) was added K2CO3 (66 mg) and tetrabutylammonium iodide (5 mg). The mixture was stirred for 10 min at room temperature, to this, a solution of 2-(3-chloropropyl)octahydropyrano[3,4-c]-pyrrole (38 mg) in DMF (1 mL) was added. The reaction mixture was heated at 90° C. for 12 h under N2 and CH2Cl2 (100 mL) was added. Then the mixture was washed with water followed by brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound (40 mg, 43.95%), HPLC: 98.50%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 488.0 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.26-1.29 (m, 2H), 1.37 (s, 3H), 2.33-2.37 (m, 3H), 2.59 (s, 1H), 3.03 (s, 1H), 3.44-3.47 (m, 1H), 3.50 (s, 1H), 3.72 (d, J=3.28 Hz, 1H), 3.78 (d, J=1.76 Hz, 1H), 3.81 (s, 1H), 3.87-3.89 (m, 1H), 3.99 (s, 3H), 4.50-4.55 (m, 2H), 7.11 (t, J=17.68 Hz, 1H), 7.25 (d, J=15.28 Hz, 1H), 7.35 (m, 1H), 7.82-7.86 (m, 1H), 8.13 (s, 1H), 8.22-8.25 (m, 1H), 8.63 (s, 1H), 8.92 (s, 1H) ppm.

Workup

  1. temperatureThe reaction mixture was heated at 90° C. for 12 h under N2
  2. washThen the mixture was washed with water
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-52585191c18c4a358f11339ec69ad9c6
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

Loading…