HCID 57474473, compound → HCID 178511927, compound

HRID 2043542Notes

Reaction equation

HRID 2043542 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([N+:19]([O-])=O)[CH:17]=3)[CH:12]=[CH:11]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.I.CS[C:25]([C:27]1[S:28][CH:29]=[CH:30][CH:31]=1)=[NH:26]>[Pd].C(O)C>[N:1]1([CH2:7][CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH:19][C:25]([C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)=[NH:26])[CH:17]=3)[CH:12]=[CH:11]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 57474473HCID 57474473, compoundHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178511927HCID 178511927, compoundYield 92.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Procedure

A solution of compound 149 (2.0 g, 6.912 mmol) in abs. ethanol (20 mL) was treated with Pd—C (0.25 g), purged with hydrogen gas and stirred for overnight (15 h) under hydrogen atm. (balloon pressure). The reaction mixture was filtered through a celite pad and washed with abs. ethanol (2×20 mL). The combined ethanol layer was treated with thiophene-2-carboximidothioic acid methyl ester hydroiodide (3.94 g, 13.824 mmol) and the resulting mixture was stirred for overnight (16 h) at room temperature. The solvent was evaporated and the product was precipitated with ether (250 mL). The solid was dissolved into sat. NaHCO3 sol.: CH2Cl2 (100 mL, 1:1). The org. layer was separated and aqueous layer was extracted with CH2Cl2 (2×50 mL). The combined CH2Cl2 layer was washed with brine (25 mL) and dried (Na2SO4). The solvent was evaporated and the crude product was purified by column chromatography (2M NH3 in methanol: CH2Cl2, 5:95) to obtain compound 150 (2.348 g, 92%) as a foam. 1H-NMR (DMSO-d6) δ1.83-1.91 (m, 2H), 2.19 (t, 2H, J=6.6 Hz), 2.30 (brs, 4H), 3.56 (t, 4H, J=4.8 Hz), 4.14 (t, 2H, J=6.6 Hz), 6.34-6.35 (m, 3H), 6.58 (dd, 1H, J=1.2, 8.2 Hz), 6.95 (brs, 1H), 7.09 (dd, 1H, J=3.9, 5.1 Hz), 7.21 (d, 1H, J=3.0 Hz), 7.44 (d, 1H, J=8.1 Hz), 7.59 (d, 1H, J=3.9 Hz), 7.72 (dd, 1H, J=0.9, 3.6 Hz).

Workup

  1. custompurged with hydrogen gas
  2. filtrationThe reaction mixture was filtered through a celite pad
  3. washwashed with abs
  4. stirringthe resulting mixture was stirred for overnight (16 h) at room temperature
  5. customThe solvent was evaporated
  6. customthe product was precipitated with ether (250 mL)
  7. dissolutionThe solid was dissolved into sat. NaHCO3 sol.
  8. customlayer was separated
  9. extractionaqueous layer was extracted with CH2Cl2 (2×50 mL)
  10. washThe combined CH2Cl2 layer was washed with brine (25 mL)
  11. dry with materialdried (Na2SO4)
  12. customThe solvent was evaporated
  13. customthe crude product was purified by column chromatography (2M NH3 in methanol: CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-1a2b9c78211e44eea1bb8e59b88e8834
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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