Sulfuric Acid → 5,6-Dichloroisoquinolin-3-amine

HRID 1875984Notes

Reaction equation

HRID 1875984 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:8]=[C:9]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH2:10][NH:11][C:12](=[NH:20])[CH:13](OCC)OCC.ClC1C=C2C(=CC=1Cl)C(N)=NC=C2>>[Cl:6][C:7]1[C:23]([Cl:24])=[CH:22][CH:21]=[C:9]2[C:8]=1[CH:13]=[C:12]([NH2:20])[N:11]=[CH:10]2

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 574766026,7-Dichloroisoquinolin-1-amineHCID 178471675N-(3,4-dichlorobenzyl)-2,2-diethoxyacetimidamide

Product 1

HCID 574766015,6-Dichloroisoquinolin-3-amineYield 86%

Conditions

Temperature
40 °C

Procedure

To sulfuric acid (4 mL, 75 mmol) was added N-(3,4-dichlorobenzyl)-2,2-diethoxyacetimidamide (2 g, 6.6 mmol) at room temperature. The reaction was heated to 40° C. for 49 hours. TLC and LC/MS indicated the presence of product. The reaction was cooled to room temperature and quenched with aq. NaOH (˜15 M) until the reaction mixture was ˜pH 7. The crude product was extracted with ethyl acetate (2×50 mL) and the organics were dried with MgSO4, filtered, and concentrated in vacuo to yield the product. The crude product was purified by chromatography (Biotage: 100% ethyl acetate to [90/10% ethyl acetate/MeOH]) to yield approximately a 1:1 mixture of regioisomers 6,7-dichloroisoquinolin-1-amine and 5,6-dichloroisoquinolin-3-amine (1.2 g, 5.64 mmol, 86.0% yield) as a dark yellow powder. The regioisomers were carried on without separation. 1H NMR: 1H NMR (500 MHz, DMSO-D6) δ ppm 8.90 (s, 1H), 8.83 (s, 1H), 8.12 (s, 1H), 7.89 (s, 1H), 7.84 (d, J=8.54 Hz, 1H), 7.28 (d, J=8.85 Hz, 1H), 6.83 (s, 1H), 6.58 (s, 1H), 6.48 (s, 2H), 6.25 (s, 2H). MS (LC/MS) R.T.=1.59; [M+H]+=213.0.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with aq. NaOH (˜15 M) until the reaction mixture
  3. extractionThe crude product was extracted with ethyl acetate (2×50 mL)
  4. dry with materialthe organics were dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto yield the product
  8. customThe crude product was purified by chromatography (Biotage: 100% ethyl acetate to [90/10% ethyl acetate/MeOH])
  9. customto yield approximately

Sources & evidence

ORD record
ord-1d85240185d74856961397b3e42b59da
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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