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

HRID 1254765Notes

Reaction equation

HRID 1254765 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.CN(C=O)C>[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 67007071(2R,3R)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoic acid

Product 1

HCID 670070804-cyano-N'-((2R,3R)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazideYield 82.3%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (2R,3R)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoic acid (1.0 g, 3.62 mmol), 4-cyanobenzhydrazide (590 mg, 3.66 mmol), HOBt (495 mg, 3.66 mmol) in THF:DMF (1:1) (40 mL) was added EDC (1.05 g, 5.48 mmol) and Et3N (0.80 mL, 5.74 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 (500 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,3R)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide (1.25 g, 82%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.10 (d, J=8.6 Hz, 2H), 7.93 (d, J=8.6 Hz, 2H), 7.83 (d, J=5.5 Hz, 1H), 7.71 (d, J=5.5 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 6.71 (d, J=8.4 Hz, 1H), 6.35 (d, J=7.8 Hz, 1H), 4.26 (m, 2H), 1.42 (d, J=6.3 Hz, 3H).

Workup

  1. customat room temperature
  2. customovernight
  3. customThe reaction was quenched
  4. additionby adding water
  5. extractionextracted with EtOAc (500 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-68bf4106ef7f4c11b493175cdd8d9d32
Source dataset
uspto-grants-2013_06
Patent number
US08455525B2

Reaction notes

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