Dichloromethane → N-(4-fluorophenyl)-6-(3-(hexahydrofuro[3,4-c]pyridin-5(3H)-yl)propoxy)-7-methoxyquinazolin-4-amine

HRID 712518Notes

Reaction equation

HRID 712518 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:20][CH3:21])=[C:16]([OH:19])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[CH:4][CH:3]=1.Cl[CH2:23][CH2:24][CH2:25][N:26]1[CH2:31][CH2:30][CH:29]2[CH2:32][O:33][CH2:34][CH:28]2[CH2:27]1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:20][CH3:21])=[C:16]([O:19][CH2:23][CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][CH:29]5[CH2:32][O:33][CH2:34][CH:28]5[CH2:27]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 867294684-((4-Fluorophenyl)amino)-7-methoxyquinazolin-6-olHCID 867295055-(3-Chloropropyl)octahydrofuro[3,4-c]pyridine

Product 1

HCID 71572916N-(4-fluorophenyl)-6-(3-(hexahydrofuro[3,4-c]pyridin-5(3H)-yl)propoxy)-7-methoxyquinazolin-4-amineYield 25.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-((4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (140 mg, 0.44 mmol, 1 eq), 5-(3-chloropropyl)octahydrofuro[3,4-c]pyridine (90 mg, 0.44 mmol, 1 eq) and K2CO3 (135 mg, 0.98 mmol, 2 eq) in DMF (10 mL) was heated to 80° C. and stirred overnight, then cooled to room temperature. To the resulted mixture was added 50 mL of CH2Cl2. The mixture was washed with brine (20 mL×3) and water (20 mL×2). The organic layer 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 as a yellow solid (50 mg, 25.00%), HPLC: 96.56%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 453.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.76-1.77 (2H, m), 2.24-2.48 (3H, m), 2.50-2.64 (3H, m), 2.68-2.71 (2H, m), 2.73-2.75 (2H, m), 2.96-3.03 (3H, m), 3.07-3.12 (2H, m), 3.61-3.90 (2H, m), 4.24-4.27 (2H, m), 7.02 (1H, s), 7.06-7.10 (1H, m), 7.16 (1H, s), 7.76-7.82 (1H, m), 7.82 (1H, s), 8.09-8.11 (1H, m), 8.59 (1H, s) ppm.

Workup

  1. temperaturecooled to room temperature
  2. washThe mixture was washed with brine (20 mL×3) and water (20 mL×2)
  3. dry with materialThe organic layer 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-0e49a6017dc14333bea615edd368e67f
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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