Ethylene Glycol → HCID 66711320, compound

HRID 1261886Notes

Reaction equation

HRID 1261886 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.[C:40]1([SH:46])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>[Cu]I>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([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:46][C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)[N:10]4[N:9]=3)=[CH:13][CH:14]=2)[CH2:19][CH2:20]1

Participants

7

Reactant 5

HCID 174Ethylene GlycolHCID 6228DimethylformamideHCID 7969ThiophenolHCID 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 66711320HCID 66711320, compoundYield 27.1%

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 (0.120 g, 0.310 mmol), Sodium tert-butoxide (89.5 mg, 0.931 mmol), Copper(I) iodide (4 mg, 0.02 mmol), 1,2-Ethanediol (34.7 uL, 0.623 mmol), N,N-Dimethylformamide (4.4 mL, 56 mmol), and finally Benzenethiol (32.1 uL, 0.313 mmol). The reaction was heated at 120° C. overnight. An HPLC showed 40% starting material remaining 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. The desired product was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 8% methanol). The collected fractions afforded [4-(4-Methyl-piperazin-1-yl)-phenyl]-(7-phenylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-amine as a yellow solid (35 mg, 27%). MP 155-157° C. LCMS (E/I+) 417.13 (M+H). NMR 1H (DSMO-d6)-9.33 (s, 1H), 8.97 (s, 1H), 7.43 (d, 2H, J=9.04 Hz), 7.30 (t, 2H, J=7.57 Hz), 7.18 (t, 1H, J=7.33 Hz), 7.13 (d, 2H, J=8.33 Hz), 7.01 (d, 1H, J=4.60 Hz), 6.92 (d, 1H, J=4.60 Hz), 6.74 (d, 2H, J=9.09 Hz), 3.03 (t, 4H, J=5.96 Hz), 2.44 (t, 4H, J=5.21 Hz), 2.23 (s, 3H).

Workup

  1. customwas partitioned with water and DCM
  2. customThe organic was separated
  3. washwashed with Brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe solid was filtered
  6. washwashed with DCM
  7. customThe Solvent was removed under vacuum
  8. customThe desired product was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 8% methanol)

Sources & evidence

ORD record
ord-ddd5d17e75d14baf9a56efd35a6a683b
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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