Dichloromethane → HCID 71572791, compound

HRID 712498Notes

Reaction equation

HRID 712498 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]2[O:11][CH2:12][CH2:13][O:14][CH:7]2[CH2:6]1.[Cl:15][C:16]1[CH:17]=[C:18]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:35][CH3:36])=[C:31]([OH:34])[CH:32]=3)[N:27]=[CH:26][N:25]=2)[CH:19]=[CH:20][C:21]=1[F:22].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CN(C=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:35][CH3:36])=[C:31]([O:34][CH2:2][CH2:3][CH2:4][N:5]4[CH2:10][CH2:9][CH:8]5[O:11][CH2:12][CH2:13][O:14][CH:7]5[CH2:6]4)[CH:32]=3)[N:27]=[CH:26][N:25]=2)[CH:19]=[CH:20][C:21]=1[F:22]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 104712174-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-olHCID 86729502HCID 86729502, compound

Product 1

HCID 71572791HCID 71572791, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-(3-chloropropyl)octahydro-[1,4]dioxino[2,3-c]pyridine (100 mg, 0.46 mmol, 1 eq), 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (145 mg, 0.46 mmol, 1 eq) and K2CO3 (128 mg, 0.92 mmol, 2 eq) in DMF (10 mL) was heated at 80° C. overnight under N2, 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. The residue was chromatographed with a silica gel column (20:1 (v/v) CH2Cl2/MeOH) to afford the title compound as a yellow solid (60 mg, 28.00%), HPLC: 95.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 503.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.04-2.10 (2H, m), 2.21-2.48 (3H, m), 2.60-2.63 (2H, m), 2.92-3.08 (2H, m), 3.56-3.62 (2H, m), 3.67-3.72 (1H, m), 3.76-3.82 (2H, m), 3.52-3.53 (1H, m), 3.97 (2H, s), 4.08-4.15 (2H, m), 7.10-7.15 (1H, m), 7.21 (1H, s), 7.31 (1H, s), 7.62-7.65 (1H, m), 7.93-7.94 (1H, m), 8.62 (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-689607eda8514657958574aa0c19a56d
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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