Hydrochloric Acid → (S)-1-(2-Azabicyclo[2.2.2]oct-2-yl)-2-[3-(2-benzyloxy-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-pyrrolo[2,3-b]-pyridin-5-yl]-2-methylpropan-1-one

HRID 609871

Reaction equation

HRID 609871 reaction equation
C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH2:34]([O:41][CH2:42][C@H:43]([C:45]1[C:53]2[C:48](=[N:49][CH:50]=[C:51]([C:54]([CH3:59])([CH3:58])[C:55]([OH:57])=O)[CH:52]=2)[NH:47][C:46]=1[C:60]1[CH:65]=[C:64]([CH3:66])[CH:63]=[C:62]([CH3:67])[CH:61]=1)[CH3:44])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[CH2:68]1[CH:73]2[CH2:74][NH:75][CH:70]([CH2:71][CH2:72]2)[CH2:69]1.Cl.C(N(CC)CC)C.O.[Cl-].[Na+].O>C(Cl)Cl>[CH:70]12[CH2:69][CH2:68][CH:73]([CH2:72][CH2:71]1)[CH2:74][N:75]2[C:55](=[O:57])[C:54]([C:51]1[CH:52]=[C:53]2[C:45]([C@H:43]([CH3:44])[CH2:42][O:41][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[C:46]([C:60]3[CH:61]=[C:62]([CH3:67])[CH:63]=[C:64]([CH3:66])[CH:65]=3)[NH:47][C:48]2=[N:49][CH:50]=1)([CH3:58])[CH3:59]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 92362-Azabicyclo(2.2.2)octaneHCID 2724699PyBOPHCID 15887219(S)-2-[3-(2-Benzyloxy-1-methylethyl)-2-(3,5-dimethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoic acidHCID 23713072Sodium chloride dihydrate

Product 1

HCID 53953435(S)-1-(2-Azabicyclo[2.2.2]oct-2-yl)-2-[3-(2-benzyloxy-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-pyrrolo[2,3-b]-pyridin-5-yl]-2-methylpropan-1-oneYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

PyBOP (1.51 g, 2.89 mmol) was added to a stirred mixture of (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-pyrrolo-[2,3-b]pyridin-5-yl]-2-methylpropanoic acid (1.20 g, 2.63 mmol), isoquinuclidine.HCl (0.78 g, 5.26 mmol) and triethylamine (1.47 mL, 10.5 mmol) in CH2Cl2 (26 mL) at ambient temperature. After approximately 12 h, the reaction mixture was poured into water/brine (1:1) and extracted with ethyl acetate (×3). The combined organic extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (gradient eluton; 60-75% ethyl acetate/hexanes as eluent) to give the title compound as a colourless foam (1.37 g, 95% overall).

Workup

  1. customat ambient temperature
  2. extractionextracted with ethyl acetate (×3)
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (gradient eluton; 60-75% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-801b13aa76c44f8db276258d42b7e442
Source dataset
uspto-grants-1999_12
Patent number
US05998432

Linked notes

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