Dichloromethane → HCID 71572669, compound

HRID 712503Notes

Reaction equation

HRID 712503 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].Br[CH2:24][CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][CH:30]2[CH2:33][O:34][CH2:35][CH:29]2[CH2:28]1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C>[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][CH2:24][CH2:25][CH2:26][N:27]4[CH2:32][CH2:31][CH:30]5[CH2:33][O:34][CH2:35][CH:29]5[CH2:28]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 86729506HCID 86729506, compound

Product 1

HCID 71572669HCID 71572669, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (140 mg, 0.44 mmol, 1 eq), 5-(3-bromopropyl)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 at 80° C. overnight under N2 and cooled to rt. To this, 50 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. The residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/MeOH) to afford the title compound as a yellow solid (50 mg, 25.00%), HPLC: 96.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 487.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.76-1.77 (1H, m), 2.24-2.48 (3H, m), 2.50-2.64 (2H, m), 2.68-2.71 (2H, m), 2.73-2.75 (2H, m), 2.96-3.03 (3H, m), 3.07-3.12 (1H, m), 3.61-3.90 (2H, m), 4.24-4.27 (2H, m), 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 rt
  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 purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-62cb359c61c04d7ab5ae73c304082320
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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