Methanol → 4-((1R,2R)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile

HRID 470865Notes

Reaction equation

HRID 470865 reaction equation
[C:1]([C:3]1[C:8]2[S:9][CH:10]=[CH:11][C:7]=2[C:6]([NH:12][C@H:13]([C@H:26]([OH:28])[CH3:27])[C:14]([NH:16][NH:17][C:18](=O)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:15])=[CH:5][CH:4]=1)#[N:2].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.CO>C1COCC1>[OH:28][C@H:26]([CH3:27])[C@@H:13]([NH:12][C:6]1[C:7]2[CH:11]=[CH:10][S:9][C:8]=2[C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)[C:14]1[O:15][C:18]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:17][N:16]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 67006219N'-((2R,3R)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide

Product 1

HCID 441998344-((1R,2R)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrileYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N′-((2R,3R)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide (0.56 g, 1.42 mmol) in THF (120 mL) was added PS-BEMP (1.94 g, 4.27 mmol, ˜2.2 mmol/g) and p-TsCl (275 mg, 1.44 mmol) at room temperature. The mixture was stirred at room temperature for 18 h, then methanol (5 mL) was added to quench the reaction. The resin was filtered and washed with MeOH. The combined filtrate was concentrated to give a residue, which was purified by flash chromatography to afford the title compound 4-((1R,2R)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile (229 mg, 43%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 7.98 (m, 2H), 7.85 (d, J=5.5 Hz, 1H), 7.71 (d, J=5.5 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 7.51˜7.57 (m, 3H), 6.87 (d, J=8.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 1H), 5.14 (dd, J=6.5, 8.8 Hz, 1H), 4.66 (d, J=6.0 Hz, 1H), 4.58 (m, 1H), 1.49 (d, J=6.2 Hz, 3H).

Workup

  1. customto quench
  2. customthe reaction
  3. filtrationThe resin was filtered
  4. washwashed with MeOH
  5. concentrationThe combined filtrate was concentrated
  6. customto give a residue, which
  7. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-0c8a8ee019ae438ea1c6a6ca267a7271
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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