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

HRID 929040Notes

Reaction equation

HRID 929040 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 962WaterSolvent

Procedure

To a solution of methyl 4-amino-5-(benzylthio)-3-fluoro-2-((2-fluorophenyl)amino)benzoate (2.07 g, 5.17 mmol) in acetic acid (60 mL) was added con. HCl (8 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. in 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 phase was washed with water (30 mL) 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 8.74 (s, 1H), 8.57 (s, 1H), 7.08 (m, 4H), 4.03 (s, 3H).

Workup

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

Sources & evidence

ORD record
ord-c5f6bc82685f45de838883e21e48958e
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

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