Tetrabutylammonium Fluoride → 4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrile

HRID 1254763Notes

Reaction equation

HRID 1254763 reaction equation
[Si]([O:8][C@@H:9]([CH3:36])[C@@H:10]([NH:24][C:25]1[C:33]2[CH:32]=[CH:31][S:30][C:29]=2[C:28]([C:34]#[N:35])=[CH:27][CH:26]=1)[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:22]([C:19]1[CH:20]=[CH:21][C:16]([C:13]2[O:12][C:11]([C@H:10]([NH:24][C:25]3[C:33]4[CH:32]=[CH:31][S:30][C:29]=4[C:28]([C:34]#[N:35])=[CH:27][CH:26]=3)[C@@H:9]([OH:8])[CH3:36])=[N:15][N:14]=2)=[CH:17][CH:18]=1)#[N:23]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 670061894-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile

Product 1

HCID 441997124-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrileYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile (355 mg, 0.69 mmol) in THF (33 mL) was added TBAF (0.70 mL, 0.70 mmol, 1 M solution in THF) at −50° C. After addition, the reaction mixture was stirred between −30° C. to −50° C. for 2 h, then quenched by adding saturated aqueous NH4Cl solution (10 mL) and extracted with EtOAc. The EtOAc extracts were washed with water, brine, dried over Na2SO4. The solvent was removed to provide a residue, which was subjected to flash chromatography purification to give the title compound 4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrile (173 mg, 63%) and some dehydration product 4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)prop-1-enylamino)benzo[b]thiophene-7-carbonitrile (70 mg, 27%). Title compound: 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.16 (d, J=8.8 Hz, 2H), 7.95 (d, J=8.8 Hz, 2H), 7.87 (d, J=5.7 Hz, 1H), 7.72 (d, J=5.7 Hz, 1H), 7.62 (d, J=8.2 Hz, 1H), 6.83 (d, J=8.2 Hz, 1H), 6.48 (d, J=8.6 Hz, 1H), 5.25 (dd, J=4.3, 8.6 Hz, 1H), 4.79 (b, 1H), 4.66 (m, 1H), 1.42 (d, J=6.3 Hz, 3H). Dehydration product: 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.25 (d, J=8.2 Hz, 2H), 8.01 (d, J=8.2 Hz, 2H), 7.96 (d, J=5.5 Hz, 1H), 7.81 (d, J=5.5 Hz, 1H), 7.61 (d, J=8.2 Hz, 1H), 7.09 (q, J=7.0 Hz, 1H), 6.58 (d, J=8.2 Hz, 1H), 1.95 (d, J=7.0 Hz, 3H).

Workup

  1. additionAfter addition
  2. customquenched
  3. additionby adding saturated aqueous NH4Cl solution (10 mL)
  4. extractionextracted with EtOAc
  5. washThe EtOAc extracts were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed
  8. customto provide a residue, which
  9. customwas subjected to flash chromatography purification

Sources & evidence

ORD record
ord-619037f0fb024a46995226d4ba3823fe
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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