Ethylene Glycol → (4-Morpholin-4-yl-phenyl)-[7-(pyridin-4-ylsulfanyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

HRID 1262260Notes

Reaction equation

HRID 1262260 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][O:21][CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].C(O)CO.CN(C)C=O.[N:39]1[CH:44]=[CH:43][C:42]([SH:45])=[CH:41][CH:40]=1>[Cu]I>[N:18]1([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:8]3[N:7]=[CH:6][C:5]4=[CH:4][CH:3]=[C:2]([S:45][C:42]5[CH:43]=[CH:44][N:39]=[CH:40][CH:41]=5)[N:10]4[N:9]=3)=[CH:13][CH:14]=2)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1

Participants

7

Reactant 5

HCID 174Ethylene GlycolHCID 6228DimethylformamideHCID 23676156Sodium t-butoxideHCID 54578326(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(4-morpholin-4-yl-phenyl)-amineHCID 178418431pyridine-4-thiol

Product 1

HCID 66711749(4-Morpholin-4-yl-phenyl)-[7-(pyridin-4-ylsulfanyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
135 °C

Procedure

Into a sealed tube, (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(4-morpholin-4-yl-phenyl)-amine (0.174 g, 0.465 mmol), Sodium tert-butoxide (134 mg, 1.40 mmol), Copper(I) iodide (8.8 mg, 0.046 mmol), 1,2-Ethanediol (52.1 uL, 0.934 mmol), N,N-Dimethylformamide (6.5 mL, 84 mmol), and Pyridine-4-thiol (0.207 g, 1.86 mmol) were added. The reaction was heated at 135° C. for 2 days. The solvent was removed under vacuum. The reaction was partitioned with water and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum to give a yellow solid. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN as eluant (5 to 35% ACN). The collected fractions were lyophilized to give a yellow solid. (33 mg, 14%). LCMS (E/I+) 405.7 (M+H). NMR 1H (DMSO-d6)-9.25 (s, 1H), 9.10 (s, 1H), 8.56 (bs, 1H), 7.40 (d, 2H, J=6.68 Hz), 7.33 (d, 2H, J=8.91 Hz), 7.19 (d, 1H, J=4.45 Hz), 7.04 (d, 1H, J=4.45 Hz), 6.70 (d, 2H, J=9.65 Hz), 3.74 (t, 4H, J=5.08 Hz), 302 (t, 4H, J=5.08 Hz).

Workup

  1. customThe solvent was removed under vacuum
  2. customThe reaction was partitioned with water and DCM
  3. customThe organic was separated
  4. washwashed with Brine
  5. dry with materialdried over Na2SO4
  6. filtrationThe solid was filtered
  7. washwashed with DCM
  8. customThe solvent was removed under vacuum
  9. customto give a yellow solid
  10. customThe reaction mixture was purified via HPLC
  11. customto give a yellow solid

Sources & evidence

ORD record
ord-42c0b34190ef4188a2bf2741a08d3a82
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…