Toluene → HCID 57335032, compound

HRID 2092570Notes

Reaction equation

HRID 2092570 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](=[O:25])[CH3:24])=[CH:20][CH:19]=3)=[CH:7][CH:8]=2)[N:3]=1.[F:26][C:27]1[CH:37]=[C:36]([NH:38][C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45](B3OC(C)(C)C(C)(C)O3)=[CH:44][CH:43]=2)=[O:40])[CH:35]=[CH:34][C:28]=1[C:29]([N:31]([CH3:33])[CH3:32])=[O: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.CCO>[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:45]4[CH:46]=[CH:47][C:42]([NH:41][C:39](=[O:40])[NH:38][C:36]5[CH:35]=[CH:34][C:28]([C:29]([N:31]([CH3:33])[CH3:32])=[O:30])=[C:27]([F:26])[CH:37]=5)=[CH:43][CH:44]=4)=[N:3]3)=[CH:8][CH:7]=2)=[CH:19][CH:20]=1)(=[O:25])[CH3:24]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 67515999HCID 67515999, compoundHCID 86665774HCID 86665774, compound

Product 1

HCID 57335032HCID 57335032, compoundYield 6%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a 50 mL round bottom flask, 1-(5-(2-chloro-4-morpholino-quinazolin-7-yl)furan-2-yl)ethanone (0.1 g, 0.00028 mol), 2-fluoro-N,N-dimethyl-4-(3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureido)-benzamide (0.144 g, 0.00034 mol), cesium carbonate (0.228 g, 0.0007 mol), toluene (7 mL) and EtOH (7 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 (0.0098 g, 0.000014 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 75° C. for 3 h. The reaction mixture was cooled, diluted with chloroform, 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 4% MeOH in chloroform. The compound was further purified by prep HPLC using 10 mM ammonium acetate in water and ACN to obtain the title compound [0.01 g, 6%]. 1H NMR (400 MHz, DMSO-d6): δ 9.04 (s, 1H), 8.96 (s, 1H), 8.46 (d, J=8.4 Hz, 2H), 8.28 (s, 1H), 8.13 (d, 1H, J=8.8 Hz), 7.92 (d, J=8.4 Hz, 1H), 7.64 (d, J=8.4 Hz, 3H), 7.55-7.52 (m, 3H), 7.38 (d, J=8.0 Hz, 2H), 3.85 (s, 8H), 2.97 (s, 6H), 2.56 (s, 3H). LC-MS (ESI): Calculated mass: 622.2; Observed mass: 623.2 (RT: 0.45 min).

Workup

  1. customThe reaction mixture was degassed with nitrogen for 5-10 min
  2. customagain degassed with nitrogen for 5-10 min
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with chloroform
  5. washwashed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe organic layer was evaporated under reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified by column chromatography
  10. customThe compound was further purified by prep HPLC

Sources & evidence

ORD record
ord-0823dc2d508c4d2987ddf6db300cfef9
Source dataset
uspto-grants-2013_05
Patent number
US08440662B2

Reaction notes

Loading…