Cesium carbonate → 1-(5-Tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-ylthio)phenyl]urea

HRID 631296Notes

Reaction equation

HRID 631296 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(C1ON=C(NC(NC2C=CC=C(O[C:41]3[C:50]4[C:45](=[CH:46][C:47]([O:53][CH2:54][CH3:55])=[C:48]([O:51][CH3:52])[CH:49]=4)[N:44]=[CH:43][N:42]=3)C=2)=O)C=1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>C(O)(C)C>[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:41]3[C:50]4[C:45](=[CH:46][C:47]([O:53][CH2:54][CH3:55])=[C:48]([O:51][CH3:52])[CH:49]=4)[N:44]=[CH:43][N:42]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 566583071-(5-Tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-yloxy)phenyl]ureaHCID 668758091-(5-Tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea

Product 1

HCID 442433061-(5-Tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-ylthio)phenyl]ureaYield 48%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(5-tert-butylisoxazol-3-yl)-3-(3-mercaptophenyl)urea described in Example 44A (0.146 g 0.5 mmol), 4-chloro-7-ethoxy-6-methoxyquinazoline from Example 6B Step 1 (0.12 g, 0.5 mmol), and Cs2CO3 (0.161 mg, 0.5 mmol) in isopropanol (10 mL) was heated at 70° C. for 7 hours. It was quenched with water and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated under reduced pressure. It was purified by silica gel chromatography with EtOAc/hexane as eluant to afford 1-(5-tert-butylisoxazol-3-yl)-3-[3-(7-ethoxy-6-methoxyquinazolin-4-ylthio)phenyl]urea as solid (0.118 g, 48%). 1H NMR (300 MHz, CDCl3) δ 9.3 (br, 1H), 8.74 (s, 1H), 8.05 (s, 1H), 7.86 (s, 1H), 7.62 (d, 1H), 7.37 (m, 3H), 7.25 (1H), 5.91 (s, 1H), 4.29 (q, 2H), 4.06 (s, 3H), 1.58 (t, 3H), 1.32 (s, 9H); LC-MS (ESI) m/z 494 (M+H)+.

Workup

  1. customIt was quenched with water
  2. extractionextracted with CH2Cl2
  3. dry with materialExtracts were dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customIt was purified by silica gel chromatography with EtOAc/hexane as eluant

Sources & evidence

ORD record
ord-3c8b8c949f224048946fc4c9879b1281
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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