Acetic Acid → HCID 56970897, compound

HRID 1615481Notes

Reaction equation

HRID 1615481 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]3[CH:14]=[C:15]([C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[S:16][C:12]=3[C:11](=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.COC(OC)[N:27]([CH3:29])C.C(O)(=O)C.O.[NH2:37]N>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:13]3[CH:14]=[C:15]([C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[S:16][C:12]=3[C:11]3[NH:37][N:27]=[CH:29][C:10]=3[CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 78373Dimethylformamide dimethyl acetalHCID 56970896HCID 56970896, compound

Product 1

HCID 56970897HCID 56970897, compoundYield 98.9%

Conditions

Temperature
120 °C

Procedure

In a 100 mL round bottomed flask was placed 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6-dihydro-1-benzothiophen-7(4H)-one (60 mg, 0.2 mmol) and then suspended in 1,1-dimethoxy-N,N-dimethylmethanamine (3 mL, 20 mmol). The mixture was stirred for 6 h at 120° C. The mixture was allowed to cool to rt and then concentrated under reduced pressure. The residue was dissolved in acetic acid (5 mL, 90 mmol) and then was added hydrazine hydrate (100 uL, 2 mmol) and the mixture was stirred for 16 h at 50° C. The mixture was allowed to cool to rt and then concentrated under reduced pressure. The residue was diluted with EtOAc (50 mL) and was washed with saturated aqueous solution of NaHCO3 (50 mL), brine (50 mL), dried over anhydrous MgSO4. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by pre-packed silica gel (24 g) column chromatography eluted with a 50% to 100% EtOAc/hexane to yield target compound as an yellow solid (72 mg), which include some impurities and further purification has been performed by preparative HPLC to yield title compound (30 mg, 50%) as an yellow solid. LCMS: (FA) ES+ 364, 366; 1H NMR (400 MHz, d6-DMSO) δ ppm 12.74 (br s, 1H), 8.50-8.52 (m, 2H), 7.58-7.59 (m, 2H), 7.55 (s, 1H), 7.40 (d, 2H), 7.25 (d, 2H), 7.18 (s, 1H), 4.40 (t, 1H), 3.13-3.19 (m, 1H), 2.93 (dd, 1H).

Workup

  1. customIn a 100 mL round bottomed flask was placed
  2. temperatureto cool to rt
  3. concentrationconcentrated under reduced pressure
  4. stirringthe mixture was stirred for 16 h at 50° C
  5. temperatureto cool to rt
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was diluted with EtOAc (50 mL)
  8. washwas washed with saturated aqueous solution of NaHCO3 (50 mL), brine (50 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. customInsoluble materials were removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by pre-packed silica gel (24 g) column chromatography
  13. washeluted with a 50% to 100% EtOAc/hexane

Sources & evidence

ORD record
ord-b0bd4f0afd0f4a0c9c0f19f447414beb
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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