1,2-Dichloroethane → HCID 17981022, compound

HRID 2249495Notes

Reaction equation

HRID 2249495 reaction equation
[OH2:1].[CH:2]1[C:11]2[C:6](=[CH:7]C=CC=2)[CH:5]=[C:4]([C:12]([OH:14])=[O:13])[N:3]=1.[CH:15]1[CH:16]=[CH:17]C2N(O)N=N[C:19]=2[CH:20]=1.CC[N:27]([CH:31]([CH3:33])[CH3:32])[CH:28]([CH3:30])C.[CH2:34]([Cl:37])[CH2:35]Cl>C(Cl)Cl.O.CCOC(C)=O>[Cl:37][C:34]1[CH:35]=[CH:7][C:6]([CH2:5][CH:4]([NH:3][C:33]([C:31]2[N:27]=[CH:28][C:30]3[C:17]([CH:32]=2)=[CH:16][CH:15]=[CH:20][CH:19]=3)=[O:1])[C:12]([OH:14])=[O:13])=[CH:11][CH:2]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27367043-Isoquinolinecarboxylic acid hydrate

Product 1

HCID 17981022HCID 17981022, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of D4-chlorophenylalanine methyl ester hydrochloride (758 Mg, 3.03 mmol), 3-isoquinolinecarboxylic acid hydrate (500 mg, 2.89 mmol), HOBT (488 mg, 3.61 mmol), and DIPEA (2.51 mL, 14.45 mmol) in CH2Cl2 (30 mL) was added EDC (692 g, 3.61 mmol). The resulting mixture was stirred at room temperature overnight. The reaction mixture was poured onto a mixture EtOAc (50 mL) and water (20 mL) and the organic phase washed with water (3×), dried (Na2SO4), filtered, and concentrated to dryness. Final purification by flash chromatography (EtOAc/hexane 1:2) afforded 820 mg of desired compound as a solid. MS m/z 369.1 (M++1). B. To a solution of the above-formed ester (820 mg, 2.26 mmol) in THF (10 mL), a 1M aqueous solution of LiOH.H2O (11.3 mL, 11.3 mmol) was added and mixture stirred at room temperature for 1 h. Reaction was cooled to 0° C. and pH was adjusted to =1 upon addition of 1M HCl. Aqueous layer was extracted with EtOAc, dried (Na2SO4), and evaporated to afford 790 mg of the title compound as a solid. MS m/z 353.0 (M+−1)

Workup

  1. washthe organic phase washed with water (3×)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customFinal purification by flash chromatography (EtOAc/hexane 1:2)

Sources & evidence

ORD record
ord-51ccdafc94f743dab969ac03fd534dee
Source dataset
uspto-grants-2008_01
Patent number
US07314879B2

Reaction notes

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