Water → HCID 86661686, compound

HRID 1262187Notes

Reaction equation

HRID 1262187 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:29]2[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)=[CH:33][CH:32]=3)=[N:28]2)=[CH:23][CH:22]=1.B([C:47]1[CH:52]=[CH:51][C:50]([CH2:53][N:54]2[CH2:59][CH2:58][S:57](=[O:61])(=[O:60])[CH2:56][CH2:55]2)=[CH:49][CH:48]=1)(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[O:61]=[S:57]1(=[O:60])[CH2:58][CH2:59][N:54]([CH2:53][C:50]2[CH:51]=[CH:52][C:47]([C:21]3[N:29]4[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]5[CH:32]=[CH:33][C:34]([N:37]6[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]6)=[CH:35][CH:36]=5)=[N:28]4)=[CH:23][CH:22]=3)=[CH:48][CH:49]=2)[CH2:55][CH2:56]1

Participants

9

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 54970580(4-((1,1-Dioxidothiomorpholino)methyl)phenyl)boronic acidHCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 86661686HCID 86661686, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Palladium acetate (25.5 mg, 0.114 mmol) and triphenylphosphine (65.6 mg, 0.250 mmol) were dissolved in 1,4-dioxane (2.00 mL) and the mixture was purged with nitrogen for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (110 mg, 0.284 mmol), 4-[(4-boronophenyl)methyl]-thiomorpholine 1,1-dioxide (306 mg, 1.14 mmol), N,N-dimethylformamide (2.00 mL) and 1.50 M sodium carbonate in water (0.379 mL, 0.568 mmol) were added. The reaction mixture was heated at 90° C. overnight and then partitioned between water (50 mL) and dichloromethane (50 mL). The organic layer was washed with water (50 mL) and brine (25 mL) and then dried over Na2SO4. Purification by silica gel chromatography using a gradient of 0-10% MeOH/DCM as the eluting solvent to obtain the title compound as a yellow-brown foam (151 mg, 100%). LCMS (m/e) 532 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.69 (s, 1H), 8.13 (d, 2H, J=7.4 Hz), 7.54 (d, 2H, J=7.8 Hz), 7.41 (d, 2H, J=7.8 Hz), 7.02-6.90 (m, 3H), 6.84-6.78 (m, 1H), 6.70-6.62 (m, 1H), 3.73 (s, 2H), 3.23-3.15 (m, 4H), 3.13-3.00 (m, 8H), 2.66-2.57 (m, 4H), 2.38 (s, 3H).

Workup

  1. customthe mixture was purged with nitrogen for 10 minutes
  2. custompartitioned between water (50 mL) and dichloromethane (50 mL)
  3. washThe organic layer was washed with water (50 mL) and brine (25 mL)
  4. dry with materialdried over Na2SO4
  5. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-909aed71747644fbaa02f05ad3e6252f
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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