Cesium carbonate → 1-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea

HRID 871336Notes

Reaction equation

HRID 871336 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([SH:20])[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:28]1[C:37]2[C:32](=[CH:33][C:34]([O:43][CH3:44])=[C:35]([O:38][CH2:39][CH2:40][O:41][CH3:42])[CH:36]=2)[N:31]=[CH:30][N:29]=1>O1CCCC1>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([S:20][C:28]3[C:37]4[C:32](=[CH:33][C:34]([O:43][CH3:44])=[C:35]([O:38][CH2:39][CH2:40][O:41][CH3:42])[CH:36]=4)[N:31]=[CH:30][N:29]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 109344884-Chloro-7-methoxy-6-(2-methoxyethoxy)quinazolineHCID 668758091-(5-Tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea

Product 1

HCID 582679221-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)ureaYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(5-tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea described in Example 44A (223 mg, 0.83 mmol) was treated with cesium carbonate (325 mg, 1.0 mmol) in anhydrous tetrahydrofuran (8 mL). The mixture was stirred at room temperature for 30 minutes. 4-chloro-7-methoxy-6-(2-methoxyethoxy)quinazoline (149 mg, 0.45 mmol) from Example 15A was added to the suspension and the mixture heated to 50° C. overnight. After cooling to room temperature the mixture was concentrated under reduced pressure and the residue purified by silica gel chromatography (ethyl acetate/dichloromethane 1:1) to give 1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea (218 mg, 50%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 9.58 (s, 1H), 9.00 (s, 1H), 8.69 (s, 1H), 7.85 (s, 1H), 7.52-7.27 (m, 5H), 6.49 (s, 1H), 4.32 (bs, 2H), 4.00 (s, 3H), 3.77 (bs, 2H), 3.36 (s, 3H), 1.27 (s, 9H); LC-MS (ESI) m/z 524 (M+H)+.

Workup

  1. temperaturethe mixture heated to 50° C. overnight
  2. temperatureAfter cooling to room temperature the mixture
  3. concentrationwas concentrated under reduced pressure
  4. customthe residue purified by silica gel chromatography (ethyl acetate/dichloromethane 1:1)

Sources & evidence

ORD record
ord-f100f4230b4443b4817d8c434d7770aa
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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