Sulfuric Acid → 7-Chloro-8-fluoroisoquinolin-3-amine

HRID 1876009Notes

Reaction equation

HRID 1876009 reaction equation
[Cl:1][C:2]1[C:3]([F:19])=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH2:5][NH:6][C:7](=[NH:15])[CH:8](OCC)OCC.S(=O)(=O)(O)O>>[Cl:1][C:2]1[C:3]([F:19])=[C:4]2[C:16]([CH:8]=[C:7]([NH2:15])[N:6]=[CH:5]2)=[CH:17][CH:18]=1

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 178471672N-(3-chloro-2-fluorobenzyl)-2,2-diethoxyacetimidamide

Product 1

HCID 534189257-Chloro-8-fluoroisoquinolin-3-amineYield 88%

Conditions

Temperature
40 °C

Procedure

To N-(3-chloro-2-fluorobenzyl)-2,2-diethoxyacetimidamide (0.97 g, 3.36 mmol) was added sulfuric acid (4 mL, 75 mmol). The reaction was heated to 40° C. for 28 hours. The reaction was cooled to room temperature and quenched with aq. sodium hydroxide (˜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. The crude product was purified by chromatography (Biotage: 100% ethyl acetate to 90/10% ethyl acetate/MeOH) to yield 7-chloro-8-fluoroisoquinolin-3-amine (0.58 g, 2.95 mmol, 88% yield) as a powder. 1H NMR (500 MHz, DMSO-d6) d ppm 8.97 (s, 1H), 7.47-7.57 (m, 1H), 7.38-7.45 (m, 1H), 6.67 (s, 1H), 6.33 (s, 2H). MS (LC/MS) R.T.=1.18; [M+H]+=196.95.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with aq. sodium hydroxide (˜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. customThe crude product was purified by chromatography (Biotage: 100% ethyl acetate to 90/10% ethyl acetate/MeOH)

Sources & evidence

ORD record
ord-83cd147e62d64c048a540dbd5deb036c
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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