Hydrochloric Acid → Methyl 4-fluoro-5-((2-fluorophenyl)amino)benzo[d][1, 2,3]thiadiazole-6-carboxylate

HRID 929051Notes

Reaction equation

HRID 929051 reaction equation
[NH2:1][C:2]1[C:11]([S:12]CC2C=CC=CC=2)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[F:27])[C:3]=1[F:28].Cl.[N:30]([O-])=O.[Na+].C([O-])(O)=O.[Na+]>C(O)(=O)C.O>[F:28][C:3]1[C:2]2[N:1]=[N:30][S:12][C:11]=2[CH:10]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[C:4]=1[NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[F:27]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 89704879HCID 89704879, compound

Product 1

HCID 89705382Methyl 4-fluoro-5-((2-fluorophenyl)amino)benzo[d][1, 2,3]thiadiazole-6-carboxylateYield 92.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

To a solution of methyl 4-amino-5-(benzylthio)-3-fluoro-2-((2-fluoro-phenyl)amino)benzoate (2.07 g, 5.17 mmol) in acetic acid (60 mL) was added HCl (con., 8 mL) and water (6 mL). The resultant was stirred at ambient temperature for 1 h. A solution of NaNO2 (0.43 g, 6.21 mmol) in water (10 mL) was added dropwisely at 0° C. within 20 min. After stirring for 3 h, the reaction was treated with saturated NaHCO3 (aq.) till the solution was neutral. The aqueous layer was extracted with ethyl acetate (30 mL×3). The combined organic extract was washed with water (30 mL×3) and brine (30 mL) sequentially, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 5:1, v/v) to give the corresponding product (yellow solid, 1.53 g, 92.1% yield). 1H NMR (400 MHz, CDCl3): δ 8.65 (s, 1H), 8.48 (s, 1H), 7.00-6.90 (m, 4H), 3.94 (s, 3H).

Workup

  1. stirringAfter stirring for 3 h
  2. extractionThe aqueous layer was extracted with ethyl acetate (30 mL×3)
  3. extractionThe combined organic extract
  4. washwas washed with water (30 mL×3) and brine (30 mL) sequentially
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 5:1
  9. customv/v) to give the corresponding product (yellow solid, 1.53 g, 92.1% yield)

Sources & evidence

ORD record
ord-8ce3f076007d47b6ac6dad371127b50d
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

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