Toluene → HCID 57335031, compound

HRID 517474Notes

Reaction equation

HRID 517474 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[N:11]=[CH:10][C:9]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[CH:8][C:6]=2[N:7]=1.[F:24][C:25]1[C:30]([F:31])=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:26]=1[NH:41][C:42](=[O:55])[NH:43][C:44]1[CH:54]=[CH:53][C:47]([C:48]([N:50]([CH3:52])[CH3:51])=[O:49])=[CH:46][CH:45]=1.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>[F:24][C:25]1[C:30]([F:31])=[C:29]([C:2]2[N:3]=[C:4]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:5]3[N:11]=[CH:10][C:9]([C:12]4[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=4)=[CH:8][C:6]=3[N:7]=2)[CH:28]=[CH:27][C:26]=1[NH:41][C:42](=[O:55])[NH:43][C:44]1[CH:54]=[CH:53][C:47]([C:48]([N:50]([CH3:52])[CH3:51])=[O:49])=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 67516241HCID 67516241, compoundHCID 86665775HCID 86665775, compound

Product 1

HCID 57335031HCID 57335031, compoundYield 11%

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-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,2-d]pyrimidin-4-yl)morpholine (0.1 g, 0.0003 mol), 4-(3-(2,3-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureido)-N,N-dimethyl-benzamide (0.16 g, 0.00036 mol), cesium carbonate (0.244 g, 0.00075 mol), toluene (7 mL), 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 (0.0105 g, 0.000015 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 75° C. for 3 h. To the cooled reaction mixture, ice cold water was added to obtain the solid. The crude product was obtained by the filtration of the solid. The crude product was purified by column chromatography using 60-120 silica gel and 4% MeOH in chloroform to isolate the product. The isolated product was washed with MeOH and filtered. The compound was further purified by prep TLC using 7% MeOH in chloroform to yield the title compound [0.02 g, 11%]. 1H NMR (400 MHz, DMSO-d6): δ 9.38 (brs, 1H), 9.09 (d, J=2.0 Hz, 1H), 9.01 (brs, 1H), 8.53 (s, 1H), 8.32 (d, J=2.0 Hz, 1H), 8.24 (s, 1H), 8.14-7.97 (m, 2H), 7.54 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.4 Hz, 2H), 4.49 (brs, 4H), 3.92 (s, 3H), 3.81 (brs, 1H), 2.96 (s, 6H). LC-MS (ESI): Calculated mass: 613.2; Observed mass: 614.2 (RT: 0.63 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, ice cold water
  4. additionwas added
  5. customto obtain the solid
  6. customThe crude product was obtained by the filtration of the solid
  7. customThe crude product was purified by column chromatography
  8. customto isolate the product
  9. washThe isolated product was washed with MeOH
  10. filtrationfiltered
  11. customThe compound was further purified by prep TLC

Sources & evidence

ORD record
ord-67ca4a512fe7468a9e37780996fdd84c
Source dataset
uspto-grants-2015_08
Patent number
US09115092B2

Reaction notes

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