1,2-Dichloroethane → (E)-2-[2-(1H-indazol-3-yl)vinyl]-N-(thiophen-2-ylmethyl)benzamide

HRID 1821346Notes

Reaction equation

HRID 1821346 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14]([OH:16])=O)=[N:2]1.CN1CCOCC1.[NH2:28][CH2:29][C:30]1[S:31][CH:32]=[CH:33][CH:34]=1.C(Cl)CCl>C1COCC1.C(OCC)(=O)C.O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14]([NH:28][CH2:29][C:30]2[S:31][CH:32]=[CH:33][CH:34]=2)=[O:16])=[N:2]1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 34005(2-Thienylmethyl)amineHCID 57586985(E)-2-[2-(1H-indazol-3-yl)vinyl]benzoic acid

Product 1

HCID 68997972(E)-2-[2-(1H-indazol-3-yl)vinyl]-N-(thiophen-2-ylmethyl)benzamideYield 23.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (E)-2-[2-(1H-indazol-3-yl)vinyl]benzoic acid (35 mg, 0.13 mmol) obtained in Step 1 of Example 47 in THF (1.0 mL) was sequentially added with 4-methylmorpholine (29 μL, 0.27 mmol), 2-(aminomethyl)thiophene (23 mg, 0.28 mmol) and EDC (36 mg, 0.19 mmol) and stirred at room temperature for 1.0 hour. The reaction mixture was added with water and ethyl acetate to separate the mixture into organic layer and aqueous layer and the organic layer was concentrated under reduced pressure. The residue was purified by silica gel chromatography (chloroform/methanol=100/0 to 90/10) and the obtained compound was crystallized from a mixed solvent of hexane/ethyl acetate (9/1, 1.0 mL) to obtain Compound 141 (11 mg, 17%).

Workup

  1. customto separate the mixture into organic layer and aqueous layer
  2. concentrationthe organic layer was concentrated under reduced pressure
  3. customThe residue was purified by silica gel chromatography (chloroform/methanol=100/0 to 90/10)
  4. customthe obtained compound was crystallized from a mixed solvent of hexane/ethyl acetate (9/1, 1.0 mL)

Sources & evidence

ORD record
ord-5aa7cf654ae34db2b15be1516d708962
Source dataset
uspto-grants-2009_10
Patent number
US07605272B2

Reaction notes

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