Eletriptan → (R)-1-acetyl-5-(benzenesulfonylethenyl)-3-(N-methyl-pyrrolidin-2-ylmethyl)-1H-indole

HRID 1182391Notes

Reaction equation

HRID 1182391 reaction equation
CN1[C@@H](CC2C3C=C(CCS(C4C=CC=CC=4)(=O)=O)C=CC=3NC=2)CCC1.[C:28]([N:31]1[C:39]2[C:34](=[CH:35][C:36]([CH2:40][CH2:41][S:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)(=[O:44])=[O:43])=[CH:37][CH:38]=2)[C:33]([CH2:51][C@H:52]2[CH2:56][CH2:55][CH2:54][N:53]2[CH3:57])=[CH:32]1)(=[O:30])[CH3:29].BrC1C=C2C(=CC=1)NC=C2C[C@H]1CCCN1C.C(N1C2C(=CC(Br)=CC=2)C(C[C@H]2CCCN2C)=C1)(=O)C.C(S(C1C=CC=CC=1)(=O)=O)=C>[Pd]>[C:28]([N:31]1[C:39]2[C:34](=[CH:35][C:36]([CH:40]=[CH:41][S:42]([C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)(=[O:43])=[O:44])=[CH:37][CH:38]=2)[C:33]([CH2:51][C@H:52]2[CH2:56][CH2:55][CH2:54][N:53]2[CH3:57])=[CH:32]1)(=[O:30])[CH3:29]

Participants

7

Reactant 5

HCID 77993Eletriptan2×HCID 79664Phenyl vinyl sulfoneHCID 10180721(R)-1-acetyl-5-(2-benzenesulphonylethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indoleHCID 11185464(R)-5-Bromo-3-(1-methyl-2-pyrrolidinyl methyl)-1H-indoleHCID 11771997(R)-1-(5-Bromo-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indol-1-yl)ethanone

Product 1

HCID 54067212(R)-1-acetyl-5-(benzenesulfonylethenyl)-3-(N-methyl-pyrrolidin-2-ylmethyl)-1H-indole

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

As a result of this difficulty, we have now developed an alternative route to eletriptan which avoids the use of a precursor which is prone to dimerisation. Specifically, the process of the invention comprises the preparation of eletriptan by the hydrolysis of (R)1-acetyl-5-(2-benzenesuiphonylethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole, which compound may conveniently be prepared by (i) N-acetylating (R)-5-bromo-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole, (ii) reacting the resulting (R)-1-acetyl-5-bromo-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole with phenyl vinyl sulphone in the presence of a palladium catalyst, a triarylphosphine and a base to give (R)-1-acetyl-5-(2-benzenesulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1 H-indole and (iii) catalytically reducing same.

Workup

  1. customAs a result of this difficulty, we

Sources & evidence

ORD record
ord-a98235405b7c45c4918c6a26b0a5fce8
Source dataset
uspto-grants-2007_10
Patent number
US07288662B2

Reaction notes

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