(1-Bromoethyl)benzene → {(R)-7-[5-(1-Phenyl-ethyl)-[1,2,3]triazol-1-yl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}-acetic acid

HRID 1944046Notes

Reaction equation

HRID 1944046 reaction equation
[N:1]([CH:4]1[CH2:23][N:8]2[C:9]3[C:14]([C:15]([CH2:16][C:17]([O:19]CCC)=[O:18])=[C:7]2[CH2:6][CH2:5]1)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[N+:2]=[N-:3].[CH3:24][CH:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:26]#[CH:27].BrC(C1C=CC=CC=1)C.C([Si](C)(C)C)#C.[N-]=[N+]=[N-]>>[C:28]1([CH:25]([C:26]2[N:1]([C@H:4]3[CH2:23][N:8]4[C:9]5[C:14]([C:15]([CH2:16][C:17]([OH:19])=[O:18])=[C:7]4[CH2:6][CH2:5]3)=[CH:13][CH:12]=[CH:11][CH:10]=5)[N:2]=[N:3][CH:27]=2)[CH3:24])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 5

HCID 11454(1-Bromoethyl)benzeneHCID 33558Azide2×HCID 66111TrimethylsilylacetyleneHCID 575422(1-Methyl-2-propynyl)benzeneHCID 59487226Propyl (7-azido-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate

Product 1

HCID 68508826{(R)-7-[5-(1-Phenyl-ethyl)-[1,2,3]triazol-1-yl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}-acetic acid

Procedure

The title compound was prepared using procedures described in EXAMPLE 8 from both enantiomerically pure propyl (7-azido-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate and (1-methylprop-2-yn-1-yl)benzene prepared from (1-bromoethyl)benzene and ethynyltrimethylsilane. The resulting diastereoisomeric esters derived from the chiral azide with the retention time of 10.3 min from EXAMPLE 6 were separated by flash chromatography using a gradient of 10-70% EA/Hex to afford after standard hydrolysis EXAMPLE 29.1 and 29.2. The resulting diastereoisomeric esters derived from the chiral azide with the retention time of 11.5 min from EXAMPLE 6 were separated by flash chromatography using a gradient of 10-70% EA/Hex to afford after standard hydrolysis EXAMPLE 29.3 and 29.4 respectively. MS (+ESI) m/z: 405.1.

Workup

  1. customwere separated by flash chromatography
  2. customto afford
  3. customafter standard hydrolysis EXAMPLE 29.1 and 29.2
  4. customwere separated by flash chromatography
  5. customto afford
  6. customafter standard hydrolysis EXAMPLE 29.3 and 29.4 respectively

Sources & evidence

ORD record
ord-d425c3c4cc704ad799feff35578f0f84
Source dataset
uspto-grants-2013_03
Patent number
US08394819B2

Reaction notes

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