4-Bromo-2-(4-fluorophenyl)-3-(pyridin-4-yl)thiophene → (S)-2-(4-Fluorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)thiophene

HRID 9882Notes

Reaction equation

HRID 9882 reaction equation
Br[C:2]1[C:3]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[S:5][CH:6]=1.BrC1C(C2C=CN=CC=2)=C(C2C=CC(F)=CC=2)NN=1.[CH2:39]1[C@@H:47]2[N:42]([CH2:43][CH2:44][C:45](=O)[CH2:46]2)[CH2:41][CH2:40]1>>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:4]2[S:5][CH:6]=[C:2]([C:45]3[CH2:46][C@H:47]4[N:42]([CH2:41][CH2:40][CH2:39]4)[CH2:43][CH:44]=3)[C:3]=2[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[CH:8][CH:9]=1

Participants

4

Reactant 3

HCID 219884994-Bromo-2-(4-fluorophenyl)-3-(pyridin-4-yl)thiopheneHCID 45087810(S)-1,2,3,5,6,7,8,8a-octahydroindolizin-7-oneHCID 178418951HCID 178418951, compound

Product 1

HCID 69371399(S)-2-(4-Fluorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)thiopheneYield 23%

Procedure

Following a procedure similar to that described in Example 2-2), but using 4-bromo-2-(4-fluorophenyl)-3-(pyridin-4-yl)thiophene prepared as described in 5) instead of 3-bromo-5-(4-fluorophenyl)-4-(pyridin-4-yl)pyrazole, and using (S)-1,2,3,5,6,7,8,8a-octahydroindolizin-7-one instead of (±)-1,2,3,5,6,7,8,8a-octahydroindolizin-7-one, the resulting product was subjected to a dehydration reaction as described in Example 3 and then treated by column chromatography through silica gel (eluent, ethyl acetate:methanol:isopropylamine=10:10:1), to give the title compound (Rf=0.50, 263 mg) as a brown amorphous solid (yield 23%).

Workup

  1. customprepared
  2. customthe resulting product was subjected to a dehydration reaction
  3. additiontreated by column chromatography through silica gel (eluent, ethyl acetate:methanol:isopropylamine=10:10:1)

Sources & evidence

ORD record
ord-b728612b8f384ff9a46a02296031b4b0
Source dataset
uspto-grants-2006_08
Patent number
US07091352B2

Reaction notes

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