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

HRID 2388581Notes

Reaction equation

HRID 2388581 reaction equation
[Cl:1][C:2]1[C:3]2[C:10]([NH:11][C@H:12]([C@@H:27]([OH:29])[CH3:28])[C:13]([NH:15][NH:16][C:17](=O)[C:18]3[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=3)=[O:14])=[CH:9][CH:8]=[C:7]([C:30]#[N:31])[C:4]=2[S:5][CH:6]=1.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.CO>C1COCC1>[Cl:1][C:2]1[C:3]2[C:10]([NH:11][C@@H:12]([C:13]3[O:14][C:17]([C:18]4[CH:19]=[CH:20][C:21]([C:24]#[N:25])=[CH:22][CH:23]=4)=[N:16][N:15]=3)[C@@H:27]([OH:29])[CH3:28])=[CH:9][CH:8]=[C:7]([C:30]#[N:31])[C:4]=2[S:5][CH:6]=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 68546596N'-((2R,3S)-2-(3-chloro-7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide

Product 1

HCID 685468493-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrileYield 9.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N′-((2R,3S)-2-(3-chloro-7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide (0.83 g, 1.83 mmol) in THF (150 mL) was added PS-BEMP (2.5 g, 5.50 mmol, ˜2.2 mmol/g) and p-TsCl (383 mg, 2.00 mmol) at room temperature. The mixture was stirred at room temperature overnight, then methanol (5 mL) was added to quench the reaction. The resin was filtered and washed with MeOH (400 mL). The combined filtrate was concentrated to give a residue, which was purified by flash chromatography to afford the title compound 3-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrile (75.2 mg, 9%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.20 (d, J=8.3 Hz, 2H), 8.00 (d, J=8.3 Hz, 2H), 7.75 (s, 1H), 7.68 (d, J=8.2 Hz, 1H), 7.65 (d, J=8.6 Hz, 1H), 6.81 (d, J=8.6 Hz, 1H), 5.28 (dd, J=2.4, 8.2 Hz, 1H), 4.93 (d, J=4.3 Hz, 1H), 4.72 (m, 1H), 1.50 (d, J=6.3 Hz, 3H).

Workup

  1. customto quench
  2. customthe reaction
  3. filtrationThe resin was filtered
  4. washwashed with MeOH (400 mL)
  5. concentrationThe combined filtrate was concentrated
  6. customto give a residue, which
  7. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-847d01c41b8e4226b792a897144c832b
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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