1,2-Dichloroethane → 4-cyano-N'-((2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide

HRID 563311Notes

Reaction equation

HRID 563311 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:17]([OH:19])[CH3:18])[C:14]([OH:16])=O)=[CH:5][CH:4]=1)#[N:2].[C:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][NH2:29])=[O:27])=[CH:24][CH:23]=1)#[N:21].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>C1COCC1>[C:20]([C:22]1[CH:23]=[CH:24][C:25]([C:26]([NH:28][NH:29][C:14](=[O:16])[C@H:13]([NH:12][C:6]2[C:7]3[CH:11]=[CH:10][S:9][C:8]=3[C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[C@@H:17]([OH:19])[CH3:18])=[O:27])=[CH:30][CH:31]=1)#[N:21]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 4567324-CyanobenzohydrazideHCID 67006652(2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoic acid

Product 1

HCID 670062524-cyano-N'-((2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazideYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoic acid (0.66 g, 2.39 mmol), 4-cyanobenzhydrazide (390 mg, 2.42 mmol), HOBt (327 mg, 2.42 mmol) in THF (40 mL) was added EDC (696 mg, 3.63 mmol) and Et3N (0.56 mL, 4.02 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min., then at room temperature overnight. The reaction was quenched by adding water and extracted with EtOAc (400 mL). The EtOAc extracts were washed with water, brine and dried over Na2SO4. Removal of the solvent and purification of the residue gave the title compound 4-cyano-N′-((2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide (0.68 g, 68%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.09 (d, J=8.6 Hz, 2H), 7.93 (d, J=8.6 Hz, 2H), 7.81 (d, J=5.7 Hz, 1H), 7.73 (d, J=5.7 Hz, 1H), 7.67 (d, J=8.2 Hz, 1H), 6.68 (d, J=8.2 Hz, 1H), 6.21 (d, J=7.2 Hz, 1H), 4.42 (m, 1H), 4.25 (dd, J=3.9, 7.2 Hz, 1H), 1.39 (d, J=6.4 Hz, 3H).

Workup

  1. customat room temperature
  2. customovernight
  3. customThe reaction was quenched
  4. additionby adding water
  5. extractionextracted with EtOAc (400 mL)
  6. washThe EtOAc extracts were washed with water, brine
  7. dry with materialdried over Na2SO4
  8. customRemoval of the solvent and purification of the residue

Sources & evidence

ORD record
ord-baff41806c9e4fef9d2f2b06ba8c573f
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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