Methanol → 3-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,4-oxadiazol-5-yl]benzonitrile

HRID 40919Notes

Reaction equation

HRID 40919 reaction equation
C[Si](C)(C)CCOC[N:7]1[C:11]2=[N:12][CH:13]=[CH:14][C:15]([C:16]3[N:20]=[C:19]([C:21]4[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=4)[C:24]#[N:25])[O:18][N:17]=3)=[C:10]2[CH:9]=[CH:8]1.[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32].CO>[OH-].[NH4+]>[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32].[NH:7]1[C:11]2=[N:12][CH:13]=[CH:14][C:15]([C:16]3[N:20]=[C:19]([C:21]4[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=4)[C:24]#[N:25])[O:18][N:17]=3)=[C:10]2[CH:9]=[CH:8]1

Participants

6

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 574776613-[3-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,4-oxadiazol-5-yl]benzonitrile

Product 2

HCID 6422Trifluoroacetic acidYield 0.2%HCID 446254233-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,4-oxadiazol-5-yl]benzonitrileYield 43.5%

Reagents, catalysts & solvents 1

HCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
60 °C

Procedure

The crude 3-[3-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,4-oxadiazol-5-yl]benzonitrile (0.08 g, 0.0002 mol) was dissolved in TFA (3.0 mL, 0.039 mol) under nitrogen and then heated to 60° C. After heating for 2 h the reaction was allowed to cool to rt and concentrated in vacuo. The resulting residue was taken up in methanol and concentrated to remove as much of the TFA as possible. The residue was taken up in methanol (2.0 mL, 0.049 mol) and ammonium hydroxide (1 mL). This mixture was stirred at rt for 2 h and the reaction was then complete. The reaction was concentrated in vacuo to give the crude product which was purified by prep HPLC on a C-18 column eluting with a ACN:water gradient with 0.2% TFA to give the title compound (0.025 gm, 43%) (M+H)+ 288. 1H NMR (DMSO-d6) δ 12.1 (bs, 1H), 8.65(s, 1H), 8.48(d, 1H, J=6.4), 8.39(d, 1H, J=4.8), 8.16(d, 1H, J=6.4), 7.84(t, 1H, J=6.4), 7.75(d, 1H, J=4.8), 7.68(m, 1H), 6.99(m, 1H).

Workup

  1. temperatureAfter heating for 2 h the reaction
  2. temperatureto cool to rt
  3. concentrationconcentrated in vacuo
  4. concentrationconcentrated
  5. customto remove as much of the TFA as possible
  6. concentrationThe reaction was concentrated in vacuo
  7. customto give the crude product which
  8. customwas purified by prep HPLC on a C-18 column
  9. washeluting with a ACN

Sources & evidence

ORD record
ord-d4c53116845b4d4b93ec9a0827ed4831
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Reaction notes

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