Water → [7-(1,2-Dimethyl-1H-imidazol-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

HRID 1262196Notes

Reaction equation

HRID 1262196 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:22]=[C:23]([CH3:27])[N:24]([CH3:26])[CH:25]=1.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:42]3[N:47]=[CH:46][C:45]4=[CH:48][CH:49]=[C:50](B5OC(C)(C)C(C)(C)O5)[N:44]4[N:43]=3)=[CH:37][CH:36]=2)[CH2:31][CH2:30]1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCCC1.C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:26][N:24]1[CH:25]=[C:21]([C:50]2[N:44]3[C:45]([CH:46]=[N:47][C:42]([NH:41][C:38]4[CH:39]=[CH:40][C:35]([N:32]5[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]5)=[CH:36][CH:37]=4)=[N:43]3)=[CH:48][CH:49]=2)[N:22]=[C:23]1[CH3:27]

Participants

9

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 72048754-Bromo-1,2-dimethyl-1H-imidazoleHCID 57416042N-[4-(4-methylpiperazin-1-yl)phenyl]-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,1-f][1,2,4]triazin-2-amine

Product 1

HCID 66712164[7-(1,2-Dimethyl-1H-imidazol-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amineYield 23%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Palladium acetate (13.0 mg, 0.0580 mmol) and triphenylphosphine (19.0 mg, 0.0725 mmol) were placed in tetrahydrofuran (2.00 mL). The mixture was allowed to stir at room temperature for 10 minutes. 4-Bromo-1,2-dimethyl-1H-imidazole (102 mg, 0.580) was then added and the reaction was again allowed to stir for 10 minutes. [4-(4-Methyl-piperazin-1-yl)-phenyl]-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine (105 mg, 0.242 mmol) was added followed by 1.50 M sodium carbonate in water (0.645 mL, 0.967 mmol) and ethanol (2.00 mL). The reaction mixture was then heated at 80° C. overnight. The reaction was partitioned between DCM (50 mL) and water (50 mL). The organic layer was washed twice with water (50 mL) and then dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by prep-HPLC using a gradient of 10-45% AcN/water both containing 0.1% TFA as the eluting solvent. The product was then free based to obtain the title compound as a yellow solid (22 mg, 23%). m.p.=242-244° C.; LCMS (m/e) 403 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.61 (s, 1H), 7.84 (s, 1H), 7.57-7.50 (m, 2H), 7.24 (d, 1H, J=4.8 Hz), 7.02-6.95 (m, 2H), 6.80 (d, 1H, J=4.8 Hz), 6.55 (bs, 1H), 3.62 (s, 3H), 3.24-3.16 (m, 4H), 2.65-2.57 (m, 4H), 2.46 (s, 3H), 2.38 (s, 3H).

Workup

  1. stirringto stir for 10 minutes
  2. temperatureThe reaction mixture was then heated at 80° C. overnight
  3. customThe reaction was partitioned between DCM (50 mL) and water (50 mL)
  4. washThe organic layer was washed twice with water (50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification

Sources & evidence

ORD record
ord-95caf10fa33542c784c05d32a02903c9
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…