Trifluoroacetic acid → 5-((S)-2-Pyrrolidin-2-yl-3H-imidazol-4-yl)-2-[4-((S)-2-pyrrolidin-2-yl-3H-imidazol-4-yl)-phenyl]-pyrimidine

HRID 80371Notes

Reaction equation

HRID 80371 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]1[N:21](COCC[Si](C)(C)C)[C:22]([C:25]2[CH:26]=[N:27][C:28]([C:31]3[CH:36]=[CH:35][C:34]([C:37]4[NH:38][C:39]([C@@H:42]5[CH2:46][CH2:45][CH2:44][N:43]5C(OC(C)(C)C)=O)=[N:40][CH:41]=4)=[CH:33][CH:32]=3)=[N:29][CH:30]=2)=[CH:23][N:24]=1)=O)(C)(C)C>C(Cl)Cl>[NH:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]1[NH:21][C:22]([C:25]2[CH:26]=[N:27][C:28]([C:31]3[CH:36]=[CH:35][C:34]([C:37]4[NH:38][C:39]([C@@H:42]5[CH2:46][CH2:45][CH2:44][NH:43]5)=[N:40][CH:41]=4)=[CH:33][CH:32]=3)=[N:29][CH:30]=2)=[CH:23][N:24]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 24951274(S)-2-[5-(2-{4-[2-((S)-1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-phenyl}-pyrimidin-5-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 249512755-((S)-2-Pyrrolidin-2-yl-3H-imidazol-4-yl)-2-[4-((S)-2-pyrrolidin-2-yl-3H-imidazol-4-yl)-phenyl]-pyrimidineYield 36.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (8 mL) was added in one portion to a stirred solution of (S)-2-[5-(2-{4-[2-((S)-1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-phenyl}-pyrimidin-5-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.50 g, 1.98 mmol) in dry CH2Cl2 (30 mL) at room temperature. The flask was sealed and the mixture was stirred at room temperature for 16 h before the solvent(s) were removed in vacuo. The residue was taken up in methanol, filtered through a PVDF syringe filter (13 mm×0.45 μm), distributed to 8 pHPLC vials and chromatographed by HPLC (gradient elution from 10% B to 100% B over 13 min on a Phenomenex C18 column, 30×100 mm, 10 μm, where A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA). After concentration of the selected test tubes by speed vacuum evaporation, the product was dissolved in methanol and neutralized by passing the solution through an UCT CHQAX 110M75 anion exchange cartridge. There was isolated the title compound as a yellow mustard-colored solid (306.7 mg, 36% yield) upon concentration of the eluant.

Workup

  1. customThe flask was sealed
  2. customwere removed in vacuo
  3. filtrationfiltered through a PVDF syringe
  4. filtrationfilter (13 mm×0.45 μm)
  5. customchromatographed by HPLC (
  6. washgradient elution from 10% B to 100% B over 13 min on a Phenomenex C18 column, 30×100 mm, 10 μm, where A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA)
  7. customAfter concentration of the selected test tubes by speed vacuum evaporation
  8. dissolutionthe product was dissolved in methanol

Sources & evidence

ORD record
ord-d593b2e0c61543549f553b4f47b9e0a6
Source dataset
uspto-grants-2014_09
Patent number
US08846023B2

Reaction notes

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