Dichloromethane → N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(octahydroisoquinolin-2(1H)-yl)propoxy)quinazolin-4-amine

HRID 712492Notes

Reaction equation

HRID 712492 reaction equation
[CH2:1]1[CH:10]2[CH:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][NH:2]1.[Cl:11][C:12]1[CH:13]=[C:14]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:35][CH3:36])=[C:27]([O:30][CH2:31][CH2:32][CH2:33]Cl)[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:15]=[CH:16][C:17]=1[F:18].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C>[Cl:11][C:12]1[CH:13]=[C:14]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:35][CH3:36])=[C:27]([O:30][CH2:31][CH2:32][CH2:33][N:2]4[CH2:3][CH2:4][CH:5]5[CH:10]([CH2:9][CH2:8][CH2:7][CH2:6]5)[CH2:1]4)[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:15]=[CH:16][C:17]=1[F:18]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 97812DecahydroisoquinolineHCID 50742265N-(3-Chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine

Product 1

HCID 71572672N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(octahydroisoquinolin-2(1H)-yl)propoxy)quinazolin-4-amineYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of decahydroisoquinoline (200 mg, 1.44 mmol, 1 eq), N-(3-chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (570 mg, 1.44 mmol, 1 eq) and K2CO3 (238 mg, 1.70 mmol, 1.2 eq) in DMF (15 mL) was heated at 80° C. overnight and cooled to room temperature. To this, 100 mL of CH2Cl2 was added, the mixture was washed with brine (20 mL×3) and water (20 mL×2). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo and the residue was chromatographed with a silica gel column (20:1 (v/v) CH2Cl2/MeOH) to afford the title compound as a yellow solid (350 mg, 49.00%), HPLC: 90.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 499.2 (M+1); 1H NMR (CDCl3, 400 MHz) δ: 1.27-1.59 (12H, m), 1.80-1.82 (2H, m), 2.07-2.33 (2H, m), 2.40-2.51 (2H, m), 3.22-3.26 (2H, m), 4.22-4.24 (2H, m), 7.14-7.16 (1H, m), 7.23 (1H, s), 7.47 (1H, s), 7.65-7.69 (1H, m), 8.00-8.02 (1H, m), 8.64 (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. concentrationconcentrated in vacuo
  5. customthe residue was chromatographed with a silica gel column (20:1 (v/v) CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-747aeeeab3a94dca97edd1b60af22c81
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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