Thiophosgene → 2-fluoro-6-[(3-isothiocyanato-1H-pyrazol-1-yl)methyl]pyridine

HRID 1625079Notes

Reaction equation

HRID 1625079 reaction equation
[F:1][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH2:14])=[N:10]2)[CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].[C:20](Cl)(Cl)=[S:21]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([N:14]=[C:20]=[S:21])=[N:10]2)[N:7]=1

Participants

5

Reactant 3

HCID 10040ThiophosgeneHCID 516892Sodium BicarbonateHCID 866916141-[(6-fluoro-2-pyridinyl)methyl]-1H-pyrazol-3-amine

Product 1

HCID 866916152-fluoro-6-[(3-isothiocyanato-1H-pyrazol-1-yl)methyl]pyridineYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Intermediate 48 (48 mg, 0.250 mmol) was dissolved in 2 mL of DCM. 2 mL of sodium bicarbonate solution (aqueous, saturated) were added to the mixture and finally thiocarbonyl dichloride (ALDRICH, 0.019 mL, 0.250 mmol) was added dropwise. The reaction was stirred for 15 h. The crude was dissolved in 5 mL of DCM and washed with 5 mL of distilled water. Organic layer was dried over MgSO4 (anh), filtered and concentrated to dryness to give the title compound as a brown oil (45 mg, 0.192 mmol, 77%). 1H NMR (300 MHz, CDCl3) δ ppm: 7.78 (q, 1H), 7.49 (d, 1H), 6.98 (dd, 1H), 6.89 (dd, 1H), 6.22 (d, 1H); 5.26 (s, 2H). [ES+MS] m/z 235 (MH+).

Workup

  1. additionwas added dropwise
  2. washwashed with 5 mL of distilled water
  3. dry with materialOrganic layer was dried over MgSO4 (anh)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-9f7286c7ad3e48deaa242d7def8c2eb5
Source dataset
uspto-grants-2014_07
Patent number
US08779153B2

Reaction notes

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