Water → HCID 66712324, compound

HRID 1262280Notes

Reaction equation

HRID 1262280 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1.Br[C:27]1[CH:28]=[C:29]2[N:34]([CH:35]=1)[N:33]=[C:32]([NH:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)=[CH:39][CH:38]=1)[N:31]=[CH:30]2.CC1(C)C(C)(C)OB([C:58]2[CH:67]=[CH:66][CH:65]=[CH:64][C:59]=2[O:60][CH2:61][C:62]#[N:63])O1.CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:49][N:46]1[CH2:47][CH2:48][N:43]([C:40]2[CH:39]=[CH:38][C:37]([NH:36][C:32]3[N:31]=[CH:30][C:29]4=[CH:28][C:27]([C:58]5[CH:67]=[CH:66][CH:65]=[CH:64][C:59]=5[O:60][CH2:61][C:62]#[N:63])=[CH:35][N:34]4[N:33]=3)=[CH:42][CH:41]=2)[CH2:44][CH2:45]1

Participants

9

Reactant 7

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 17998915[2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]acetonitrileHCID 66712235HCID 66712235, compound

Product 1

HCID 66712324HCID 66712324, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

1155h. Into a 8-dram vial, Palladium Acetate (0.0059 g, 0.000026 mol) and Triphenylphosphine (0.019 g, 0.000074 mol) were added. The mixture was purged under an atmosphere of Nitrogen for 10 minutes. 1,4-Dioxane (2.00 mL, 0.0256 mol) was added and stirred for 10 minutes at room temperature. (6-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.102 g, 0.000264 mol), [2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-acetonitrile (0.137 g, 0.000527 mol), N,N-Dimethylformamide (4.0 mL, 0.052 mol), and 1.50 M of Sodium carbonate in Water (1.58 mL, 0.00237 mol) were added. The reaction was heated at 90° C. for 3 hours. The reaction was partitioned with water and EtOAc. The organic was separated, washed with Brine, and dried over magnesium sulfate. The solid was filtered and washed with EtOAc. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions afforded a solid. The solid was triturated with Et2O and filtered to give (2-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-6-yl}-phenoxy)-acetonitrile a yellow solid (5 mg, 3%). LCMS (E/I+) 440.18 (M+H). NMR 1H (DMSO-d6)-9.57 (s, 1H), 9.29 (s, 1H), 8.93 (s, 1H), 8.18 (s, 1H), 7.81 (d, 1H, J=7.81 Hz), 7.69 (d, 2H, J=8.19 Hz), 7.34 (t, 1H, J=7.80 Hz), 7.26 (d, 1H, J=7.80 Hz), 7.21 (s, 1H), 7.14 (t, 1H, J=7.02 Hz), 7.00 (d, 2H, J=8.19 Hz), 5.32 (s, 2H), 3.75 (d, 2H, J=12.58 Hz), 3.485-3.59 (m, 2H), 3.09-3.24 (m, 2H), 2.80-2.97 (m, 5H).

Workup

  1. custom1155h
  2. customThe mixture was purged under an atmosphere of Nitrogen for 10 minutes
  3. temperatureThe reaction was heated at 90° C. for 3 hours
  4. customThe reaction was partitioned with water and EtOAc
  5. customThe organic was separated
  6. washwashed with Brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe solid was filtered
  9. washwashed with EtOAc
  10. customThe solvent was removed under vacuum
  11. customThe reaction mixture was purified via HPLC
  12. customThe collected fractions afforded a solid
  13. customThe solid was triturated with Et2O
  14. filtrationfiltered

Sources & evidence

ORD record
ord-fc09f4b29f5842e295cc935dacee31d9
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…