Cesium carbonate → HCID 67298318, compound

HRID 1520331Notes

Reaction equation

HRID 1520331 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17](I)[CH:18]=3)[N:13]=[C:12]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[O:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][OH:35])[CH2:29][CH2:28]1.NC1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1N.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:35][CH2:34][CH2:33][N:30]4[CH2:31][CH2:32][O:27][CH2:28][CH2:29]4)[CH:18]=3)[N:13]=[C:12]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 205712,2'-Diamino-1,1'-dinaphthylHCID 611632-MorpholinoethanolHCID 67298145HCID 67298145, compound

Product 1

HCID 67298318HCID 67298318, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A 2.5 dram reaction vial was charged with N-(3-chloro-4-fluorophenyl)-6-iodo-2-(pyridin-3-yl)quinazolin-4-amine (0.250 g, 0.524 mmol), 2-morpholinoethanol (1 ml, 8.17 mmol) as solvent, copper(I) iodide (0.020 g, 0.105 mmol), racemic-2,2′-diamino-1,1′-binaphthyl (0.030 g, 0.105 mmol), and cesium carbonate (0.513 g, 1.573 mmol). The reaction mixture was heated at 110° C. overnight. After cooling, water was added to the reaction mixture, and the resultant precipitate was collected by filtration. The solid residue was purified via ISCO (silica, 12 g column, 95% dichloromethane-5% methanol-0.1% NH4OH) to yield the desired compound as a brown solid. The solid was further washed with a mixture of water and saturated NaHCO3 solution and dried. The product off the column was further purified by prep TLC (silica gel, 1000 micron, 95% dichloromethane-5% methanol-0.1% NH4OH) to afford the desired product as a light brown solid (21.2 mg, 8%), LCMS m/z=480.0 (M+1) (Method C) (retention time=2.09 min). 1H NMR (300 MHz, DMSO) δ 9.81 (s, 1H), 9.47 (d, J=1.8 Hz, 1H), 8.66-8.57 (m, 2H), 8.21 (dd, J=6.8, 2.6 Hz, 1H), 7.92 (d, J=2.5 Hz, 1H), 7.87 (ddd, J=8.9, 4.3, 2.7 Hz, 1H), 7.81 (d, J=9.1 Hz, 1H), 7.57-7.47 (m, 3H), 4.25 (t, J=5.8 Hz, 2H), 3.64-3.55 (m, 4H), 2.78 (t, J=5.7 Hz, 2H), 2.55-2.49 (m, 4H).

Workup

  1. customA 2.5 dram reaction
  2. temperatureAfter cooling
  3. filtrationthe resultant precipitate was collected by filtration
  4. customThe solid residue was purified via ISCO (silica, 12 g column, 95% dichloromethane-5% methanol-0.1% NH4OH)

Sources & evidence

ORD record
ord-f4aa098548b146248fd9844dd040a9f8
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

Loading…