Hydrogen Sulfide → ethyl ((1S)-5-{3-[4-(aminocarbonothioyl)-2-methoxyphenoxy]propoxy)-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2235890Notes

Reaction equation

HRID 2235890 reaction equation
[C:1]([C:3]1[CH:28]=[CH:27][C:6]([O:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[C@H:17]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:16][CH2:15]3)=[C:5]([O:29][CH3:30])[CH:4]=1)#[N:2].[SH2:31].C(NCC)C>CN(C=O)C>[NH2:2][C:1]([C:3]1[CH:28]=[CH:27][C:6]([O:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[C@H:17]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:16][CH2:15]3)=[C:5]([O:29][CH3:30])[CH:4]=1)=[S:31]

Participants

5

Reactant 3

HCID 402Hydrogen SulfideHCID 8021DiethylamineHCID 16110508ethyl {(1S)-5-[3-(4-cyano-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 16110447ethyl ((1S)-5-{3-[4-(aminocarbonothioyl)-2-methoxyphenoxy]propoxy)-2,3-dihydro-1H-inden-1-yl)acetateYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

Into a solution of ethyl {(1S-5-[3-(4-cyano-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl}acetate (2.2 g, 5.4 mmol) (Example 145) in DMF (anhydrous, 20 mL) under argon at rt was passed H2S gas at a moderate rate for 30 min. A solution of diethylamine (0.8 g, 8.1 mmol) in DMF (5 mL) was added in one portion, and the reaction was stirred at 60° C. for 3 h. Then the reaction was cooled to rt and argon was passed through the reaction mixture for 1 h to remove residual H2S. The reaction mixture was then concentrated under reduced pressure and the residue purified by silica gel flash chromatography (EtOAc/Hexane (v/v)=1:1) to afford 1.9 g (81%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 1.21 (t, 3H), 1.60-1.68 (m, 1H), 2.15-2.22 (m, 2H), 2.23-2.34 (m, 1H), 2.38 (q, 1H), 2.70-2.86 (m, 3H), 3.38-3.44 (m, 1H), 3.80 (s, 3H), 4.05-4.16 (m, 4H), 4.19 (t, 2H), 6.70 (d, 1H), 6.80 (s, 1H), 6.97 (d, 1H), 7.06 (d, 1H), 7.56-7.64 (m, 2H), 9.33-9.40 (s, 1H), 9.65 (s, 1H).

Workup

  1. customat rt
  2. customfor 30 min
  3. temperatureThen the reaction was cooled to rt
  4. waitargon was passed through the reaction mixture for 1 h
  5. customto remove residual H2S
  6. concentrationThe reaction mixture was then concentrated under reduced pressure
  7. customthe residue purified by silica gel flash chromatography (EtOAc/Hexane (v/v)=1:1)

Sources & evidence

ORD record
ord-33e837cbcd7646e58194bceb13f5712f
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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