Dimethylformamide → 4-(3-(4-(7-(5-cyanofuran-2-yl)-4-morpholino-quinazolin-2-yl)-3-fluorophenyl)ureido)-N,N-dimethyl-benzamide

HRID 2092568

Reaction equation

HRID 2092568 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:18]3[O:22][C:21]([C:23]#[N:24])=[CH:20][CH:19]=3)=[CH:7][CH:8]=2)[N:3]=1.[F:25][C:26]1[CH:27]=[C:28]([NH:41][C:42](=[O:55])[NH:43][C:44]2[CH:54]=[CH:53][C:47]([C:48]([N:50]([CH3:52])[CH3:51])=[O:49])=[CH:46][CH:45]=2)[CH:29]=[CH:30][C:31]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>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:23]([C:21]1[O:22][C:18]([C:6]2[CH:5]=[C:4]3[C:9]([C:10]([N:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)=[N:11][C:2]([C:31]4[CH:30]=[CH:29][C:28]([NH:41][C:42](=[O:55])[NH:43][C:44]5[CH:54]=[CH:53][C:47]([C:48]([N:50]([CH3:52])[CH3:51])=[O:49])=[CH:46][CH:45]=5)=[CH:27][C:26]=4[F:25])=[N:3]3)=[CH:8][CH:7]=2)=[CH:19][CH:20]=1)#[N:24]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 675176174-(3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureido)-N,N-dimethyl-benzamideHCID 866657725-(2-Chloro-4-morpholino-quinazolin-7-yl)furan-2-carbonitrile

Product 1

HCID 573350304-(3-(4-(7-(5-cyanofuran-2-yl)-4-morpholino-quinazolin-2-yl)-3-fluorophenyl)ureido)-N,N-dimethyl-benzamideYield 6.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL round bottom flask, 5-(2-chloro-4-morpholino-quinazolin-7-yl)furan-2-carbonitrile (0.12 g, 0.00035 mol), 4-(3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureido)-N,N-dimethyl-benzamide (0.144 g, 0.00053 mol), cesium carbonate (0.228 g, 0.0007 mol), DMF (3 mL) and water (3 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction flask, Pd(PPh3)2Cl2 (0.013 g, 0.0000175 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 2 h. To the cooled reaction mixture, water was added and extracted with ethyl acetate. The organic layer was separated, washed with water, brine and dried over anhydrous sodium sulfate. The organic layer was evaporated under reduced pressure to afford the crude product. The crude product was purified by column chromatography using 60-120 silica gel and 2-5% MeOH in chloroform to obtain the title compound [0.013 g, 6%]. 1H NMR (400 MHz, DMSO-d6): δ 9.21 (s, 1H), 9.04 (s, 1H), 8.27 (d, J=2.0 Hz, 1H), 8.19-8.13 (m, 2H), 7.93 (dd, J′=1.6, J″=8.4 Hz, 1H), 7.82 (d, J=4.0 Hz, 1H), 7.64 (d, J=3.6 Hz, 2H), 7.61 (d, J=2.0 Hz, 1H), 7.54 (d, J=8.4 Hz, 2H), 7.28 (dd, J′=8.8 Hz, J″=2.0 Hz, 2H), 3.83 (s, 8H), 2.96 (s, 6H). LC-MS (ESI): Calculated mass: 605.2; Observed mass: 606.2 (RT: 1.17 min).

Workup

  1. customThe reaction mixture was degassed with nitrogen for 5-10 min
  2. customagain degassed with nitrogen for 5-10 min
  3. customTo the cooled reaction mixture, water
  4. additionwas added
  5. extractionextracted with ethyl acetate
  6. customThe organic layer was separated
  7. washwashed with water, brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe organic layer was evaporated under reduced pressure
  10. customto afford the crude product
  11. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-a2add9335c024abc9bb7ce554ff8776e
Source dataset
uspto-grants-2013_05
Patent number
US08440662B2

Linked notes

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