Tetrahydrofuran → HCID 118159694, compound

HRID 628399Notes

Reaction equation

HRID 628399 reaction equation
[Si]([O:18][CH2:19][C:20]1[CH:21]=[C:22]([CH:54]=[C:55]([Cl:57])[CH:56]=1)[CH2:23][N:24]1[C:32]2[C:27](=[N:28][C:29]([N:33](C(OC(C)(C)C)=O)[NH:34]C(OC(C)(C)C)=O)=[CH:30][CH:31]=2)[CH:26]=[C:25]1[C:49]1[O:50][CH:51]=[N:52][N:53]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:58][CH2:59]CC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C(O)(=O)C>[Cl:57][C:55]1[CH:56]=[C:20]([CH2:19][OH:18])[CH:21]=[C:22]([CH2:23][N:24]2[C:32]3[CH:31]=[CH:30][C:29]4[N:28]([C:58]([CH3:59])=[N:34][N:33]=4)[C:27]=3[CH:26]=[C:25]2[C:49]2[O:50][CH:51]=[N:52][N:53]=2)[CH:54]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 123896102HCID 123896102, compound

Product 1

HCID 118159694HCID 118159694, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of di-tert-butyl 1-[1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]-2-(1,3,4-oxadiazol-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate (0.26 g, 0.32 mmol, from Step 3) in acetic acid (15 mL) was heated at 180° C. for 5 minutes in the microwave. Acetic acid was removed in vacuo. The residue was partitioned between an additional NaHCO3 and EtOAc. The aqueous layer was further extracted with two portions of EtOAc. The combined organic layers were dried over sodium sulfate, decanted and concentrated. The product was dissolved in THF (5 mL) and was treated with 1.0 M TBAF in THF (0.64 mL, 0.64 mmol, Aldrich). When the reaction was complete as determined by LCMS, the reaction mixture was poured into pH 7 buffer and extracted with three portions of EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-10% MeOH in DCM was used to purify the product. Yield: (0.045 g, 35%).

Workup

  1. customAcetic acid was removed in vacuo
  2. customThe residue was partitioned between an additional NaHCO3 and EtOAc
  3. extractionThe aqueous layer was further extracted with two portions of EtOAc
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. dissolutionThe product was dissolved in THF (5 mL)
  8. additionthe reaction mixture was poured into pH 7 buffer
  9. extractionextracted with three portions of EtOAc
  10. dry with materialThe combined organics were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. washFlash chromatography, eluting with a gradient from 0-10% MeOH in DCM
  14. customto purify the product

Sources & evidence

ORD record
ord-0f8ba5f140174440aaa8e6b1fac1363a
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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