Hydrochloric Acid → HCID 65564145, compound

HRID 1754341Notes

Reaction equation

HRID 1754341 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][C:10]1[N:11]=[N:12][S:13][C:14]=1[C:15](O)=[O:16].Cl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>C1COCC1.C(OCC)(=O)C.O.C(Cl)CCl>[Br:8][C:5]1[N:6]=[CH:7][C:2]([NH:1][C:15]([C:14]2[S:13][N:12]=[N:11][C:10]=2[CH3:9])=[O:16])=[N:3][CH:4]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5995392-Amino-5-bromopyrazineHCID 13819924-Methyl-1,2,3-thiadiazole-5-carboxylic acid

Product 1

HCID 65564145HCID 65564145, compoundYield 22.3%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-amino-5-bromopyrazine (1.0 g, 5.74 mmol, 1.2 eq) and 4-methyl-1,2,3-thiadiazole-5-carboxylic acid (690 mg, 4.79 mmol, 1.0 eq) in THF (20 mL) at room temperature was sequentially added EDC. HCl (970 mg, 7.18 mmol, 1.5 eq), HOBT (1.37 g, 7.18 mmol, 1.5 eq) and diisopropylethyl amine (1.23 mL, 9.58 mmol, 2.0 eq). The resulting solution was stirred at the same temperature for 24 h. Water (30 mL) was added to the reaction mixture followed by ethyl acetate (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with 1N hydrochloric acid (20 mL), saturated sodium bicarbonate solution (20 mL), brine (20 mL) dried (Na2SO4) and filtered. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel) to afford 321 mg of the desired product as a white solid. 1HNMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H, D2O exchangeable), 9.20 (s, 1H), 8.72 (s, 1H), 2.83 (s, 3H); ESI-MS (m/z) 300, 302 [(MH)+, Br79,81].

Workup

  1. customat room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layers were washed with 1N hydrochloric acid (20 mL), saturated sodium bicarbonate solution (20 mL), brine (20 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under vacuum
  8. customthe crude product was purified by flash column chromatography (silica gel)

Sources & evidence

ORD record
ord-7d4a0948643c43ccbf94242c1a7ac0b2
Source dataset
uspto-grants-2015_10
Patent number
US09169242B2

Reaction notes

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