Acetonitrile → (3'S)-1'-[4-(1H-indol-1-ylmethyl)benzoyl]-1,3'-bipyrrolidine

HRID 1163095Notes

Reaction equation

HRID 1163095 reaction equation
N=C=N.N1C2C(=CC=CC=2)C([CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)=C1.[CH:23]1[CH:24]=[CH:25][C:26]2N(O)N=[N:29][C:27]=2[CH:28]=1.[N:33]1([C@H:38]2[CH2:42][CH2:41][NH:40][CH2:39]2)[CH2:37][CH2:36][CH2:35][CH2:34]1.[CH3:43][C:44]#N>C(N(CC)CC)C>[N:29]1([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([N:40]3[CH2:41][CH2:42][C@H:38]([N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)[CH2:39]3)=[O:20])=[CH:21][CH:22]=2)[C:27]2[C:26](=[CH:25][CH:24]=[CH:23][CH:28]=2)[CH:44]=[CH:43]1

Participants

7

Reactant 5

HCID 6342Acetonitrile3×HCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 7176274(3S)-3-(Pyrrolidin-1-YL)pyrrolidineHCID 684257424-((1H-indol-3-yl)methyl)benzoic acid

Product 1

HCID 46230691(3'S)-1'-[4-(1H-indol-1-ylmethyl)benzoyl]-1,3'-bipyrrolidine

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

A solution of methyl 4-((1H-indol-3-yl)methyl)benzoate (Tet. Lett. 44 (2003) 4589-4591) (0.50 g, 1.88-mmol) in methanol is treated with an aqueous solution of NaOH (4.15 mL, 1N, 4.15 mmol), heated to reflux temperature for 3 h and concentrated in vacuo. The resultant solid residue is dissolved in H2O and acidified with HCl. The resultant precipitate is removed by filtration and dried to yield 4-((1H-indol-3-yl)methyl)benzoic acid as a white solid, 0.468 g (99%). A microwave vial is charged with PS-Carbodiimide (0.275 g, 1.2 mmol/g, 0.33 mmol). To the vial is added a solution of 4-((1H-indol-3-yl)methyl)-benzoic acid (0.070 g, 0.28 mmol) in CH3CN, a solution of HOBT (0.045 g, 0.33 mmol) in CH3CN, a solution of (S)-1,3′-bipyrrolidine (0.065 g, 0.31 mmol) in CH3CN and 0.11 mL of triethylamine. The reaction mixture is irradiated in the Emry's Optimizer at 110° C. for 6 minutes and then concentrated under reduced pressure. The resultant residue is purified by flash chromatography to yield the title product as a white solid, 0.064 g, (68%), mp 141-153° C., identified by H1 NMR and mass spectral analyses. MS (ES) m/z 372.2.

Workup

  1. customThe reaction mixture is irradiated in the Emry's Optimizer at 110° C. for 6 minutes
  2. concentrationconcentrated under reduced pressure
  3. customThe resultant residue is purified by flash chromatography

Sources & evidence

ORD record
ord-7fc68efac2f4481a99f25bca242a1106
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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