Ethylene Glycol → [7-(2-Methoxy-phenylsulfanyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

HRID 1261897Notes

Reaction equation

HRID 1261897 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.CC(C)([O-])C.[Na+].C(O)CO.CN(C)C=O.[CH3:40][O:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[SH:48]>[Cu]I>[CH3:40][O:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[S:48][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

Participants

7

Reactant 5

HCID 174Ethylene GlycolHCID 6228DimethylformamideHCID 23642ThioguaiacolHCID 23676156Sodium t-butoxideHCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66711246[7-(2-Methoxy-phenylsulfanyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Reagents, catalysts & solvents 1

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

Conditions

Temperature
120 °C

Procedure

Into a sealed tube was added (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.320 g, 0.826 mmol), Sodium tert-butoxide (238 mg, 2.48 mmol), Copper(I) iodide (16 mg, 0.083 mmol), 1,2-Ethanediol (92.6 uL, 1.66 mmol), N,N-Dimethylformamide (12 mL, 150 mmol), and finally 2-Methoxy-benzenethiol (0.174 g, 1.24 mmol). The reaction was heated at 120° C. overnight. The reaction was partitioned with DCM and water. The organic was separated, washed with Brine, and dried over magnesium sulfate. The solid was filtered and washed with DCM. The solvent was removed under vacuum. The product was isolated via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol). The collected fractions afforded [7-(2-Methoxy-phenylsulfanyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine an orange solid (9 mg, 2.5%). MP 171-172° C. LCMS (E/I+) 447.24 (M+H). NMR 1H (DSMO-d6)-9.27 (s, 1H), 8.97 (s, 1H), 7.35 (d, 2H, J=9.00 Hz), 7.08-7.20 (m, 2H), 6.97 (d, 1H, J=4.68 Hz), 6.92 (d, 1H, J=4.57 Hz), 6.75 (t, 1H, J=6.72 Hz), 6.68 (d, 2H, J=9.08 Hz), 6.36 (dd, 1H, JJ=1.40, 6.41 Hz), 3.91 (s, 3H), 3.01 (t, 4H, J=4.72 Hz), 2.43 (t, 4H, J=4.68 Hz), 2.21 (s, 3H).

Workup

  1. customThe reaction was partitioned with DCM and water
  2. customThe organic was separated
  3. washwashed with Brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe solid was filtered
  6. washwashed with DCM
  7. customThe solvent was removed under vacuum
  8. customThe product was isolated via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol)

Sources & evidence

ORD record
ord-89c6b1017e644c688341dd96ff642c37
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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