Toluene → HCID 86710173, compound

HRID 2284404Notes

Reaction equation

HRID 2284404 reaction equation
Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:20]=3)=[C:7]([F:18])[CH:8]=2)[N:3]=1.[C:29]([O:33][C:34]([NH:36][C:37]1[N:42]=[CH:41][C:40](B(O)O)=[CH:39][N:38]=1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(O)C>[F:18][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][C:6]=1[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:20]=1)[N:3]=[C:2]([C:40]1[CH:41]=[N:42][C:37]([NH:36][C:34](=[O:35])[O:33][C:29]([CH3:31])([CH3:30])[CH3:32])=[N:38][CH:39]=1)[N:11]=[C:10]2[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 45489688{2-[(tert-Butoxycarbonyl)amino]pyrimidin-5-yl}boronic acidHCID 86710172HCID 86710172, compound

Product 1

HCID 86710173HCID 86710173, compoundYield 51.7%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a 50 mL round bottom flask, 4-(2-chloro-6-fluoro-7-(3-(methylsulfonyl)phenyl)quinazolin-4-yl)morpholine (0.1 g, 0.0002 mol), (2-((tert-butoxycarbonyl)amino)pyrimidin-5-yl)boronic acid (0.085 g, 0.0003 mol), cesium carbonate (0.192 g, 0.0005 mol), toluene (5 mL), ethanol (5 mL) and water (2 mL) were added. The reaction vessel was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)2Cl2 (0.008 g, 0.000012 mol) was added and again degassed with N2 for 5-10 minutes. The reaction mixture was stirred at 75° C. for 3 hours. The reaction mixture was cooled and diluted with chloroform. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under the reduced pressure to afford the crude product. The crude product was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in n-hexane) to yield tert-butyl (5-(6-fluoro-7-(3-(methylsulfonyl)phenyl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-yl)carbamate [0.06 g, 43%]. LC-MS (ESI): Calculated mass: 580.1; Observed mass [M+H]+: 581.3 (RT=1.52 min).

Workup

  1. customThe reaction vessel was degassed with N2 for 5-10 minutes
  2. customagain degassed with N2 for 5-10 minutes
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with chloroform
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under the reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified by column chromatography (60-120 silica gel, 50% ethyl acetate in n-hexane)

Sources & evidence

ORD record
ord-c7171566ea5140cb8d8986472e83907f
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

Loading…