Water → HCID 66712504, compound

HRID 1262404Notes

Reaction equation

HRID 1262404 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[CH3:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C)C=O.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)Cl>[CH3:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[N:10]3[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]4[CH:17]=[CH:16][C:15]([N:18]5[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]5)=[CH:14][CH:13]=4)=[N:9]3)=[CH:4][CH:3]=2)=[CH:30][CH:29]=1

Participants

10

Reactant 7

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 37238124-(Methoxymethyl)benzeneboronic 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 66712504HCID 66712504, compoundYield 94.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (85 mg, 0.22 mmol), 4-Methoxymethylphenylboronic acid (72.8 mg, 0.439 mmol), Triphenylphosphine (16 mg, 0.062 mmol) and Palladium Acetate (4.9 mg, 0.022 mmol) were placed in a vial and purged with vac/N2. N,N-Dimethylformamide (4.0 mL, 52 mmol), 1,4-Dioxane (2.0 mL, 26 mmol) and 2.00 M of Sodium carbonate in Water (1.02 mL, 2.04 mmol) were added and the mixture again purged (vac/N2) before being heated to 90° C. for 3 h. The mixture was cooled, diluted with EtOAc (10 mL) and ext. w/3M HCl (3×10 mL). The aq. extr. was washed with EtOAc (10 mL), then basified with NaOH (15% w/w), giving a slurry. The slurry was extr. with DCM (3×10 mL) and the org. extr. washed with brine (10 mL), dried over sodium sulfate and conc. in vacuo to give [7-(4-Methoxymethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (89 mg, 94%). LCMS (HPLC): 0.87 min, m/z=429 (M+H); 1H-NMR (CDCl3): 8.67 (s, 1H), 8.14 (d, 2H, J=8.2 Hz), 7.55 (d, 2H, J=8.9 Hz), 7.45 (d, 2H, J=8.2 Hz), 7.00 (d, 1H, J=4.7 Hz), 6.95 (d, 2H, J=8.9 Hz), 6.81 (d, 1H, J=4.7 Hz), 6.64 (s, 1H), 4.55 (s, 2H), 3.45 (s, 3H), 3.20 (m, 4H), 2.61 (m, 4H), 2.37 (s, 3H).

Workup

  1. custompurged with vac/N2
  2. customthe mixture again purged (vac/N2)
  3. temperatureThe mixture was cooled
  4. additiondiluted with EtOAc (10 mL)
  5. washwas washed with EtOAc (10 mL)
  6. customgiving a slurry
  7. washwashed with brine (10 mL)
  8. dry with materialdried over sodium sulfate and conc. in vacuo

Sources & evidence

ORD record
ord-8fe8ede3ffe84f73bfe311a7b267f5e2
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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