Thionyl Chloride → HCID 24804764, compound

HRID 2245851Notes

Reaction equation

HRID 2245851 reaction equation
[CH2:1]([O:3][C:4]([C:6](=O)[NH:7][CH:8]([CH3:10])[CH3:9])=[O:5])[CH3:2].S(Cl)(Cl)=O.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:26][C:27]2[C:28]([C:34]([NH:36][NH2:37])=O)=[N:29][CH:30]=[C:31]([Cl:33])[CH:32]=2)(=[O:25])=[O:24])=[CH:19][C:18]=1[C:38]([F:41])([F:40])[F:39]>C1(C)C=CC=CC=1>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:26][C:27]2[C:28]([C:34]3[N:7]([CH:8]([CH3:10])[CH3:9])[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[N:37][N:36]=3)=[N:29][CH:30]=[C:31]([Cl:33])[CH:32]=2)(=[O:24])=[O:25])=[CH:19][C:18]=1[C:38]([F:39])([F:41])[F:40]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 5001766HCID 5001766, compoundHCID 59216810HCID 59216810, compound

Product 1

HCID 24804764HCID 24804764, compoundYield 3.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a vial containing ethyl(isopropylcarbamoyl)formate (160 mg, 1.0 mmol) was added thionyl chloride (1.0 mL, 13.8 mmol). The vial was capped with a teflon coated septa and heated to 80° C. for 5 h. After cooling to room temperature, the volatiles were removed in vacuo. A solution of 4-chloro-N-(5-chloro-2-(hydrazinecarbonyl)pyridine-3-yl)-3-(trifluoromethyl)benzenesulfonamide (342 mg, 0.80 mmol) in toluene (3 mL) was added. The mixture was stirred at 40° C. for 16 h. After cooling to room temperature, the toluene was removed in vacuo. Ethanol (9 mL) and triethylamine (1 mL) were added, and the solution heated to 90° C. for 4 h. After cooling to room temperature, the volatiles were removed in vacuo, and the resulting residue purified by flash chromatography on 4 g of silica gel (0→20% gradient of MeOH in DCM). The pure fractions were collected, and the solvent removed in vacuo to afford the title compound (14 mg, 3% yield). HPLC retention time=3.17 minutes. 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J=2.4, 1H), 8.19 (d, J=2.4, 1H), 8.04 (d, J=2.4, 1H), 7.89 (dd, J=2.0, 8.4, 1H), 7.53 (d, J=8.0, 1H), 5.66 (sept, J=7.0, 1H), 4.52 (q, J=7.4, 2H), 1.52 (d, J=7.0, 6H), 1.50 (t, J=7.4, 3H). MS (ES) [M+H]+ expected 552.0, found 552.0.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe volatiles were removed in vacuo
  3. temperatureAfter cooling to room temperature
  4. customthe toluene was removed in vacuo
  5. additionEthanol (9 mL) and triethylamine (1 mL) were added
  6. temperaturethe solution heated to 90° C. for 4 h
  7. temperatureAfter cooling to room temperature
  8. customthe volatiles were removed in vacuo
  9. customthe resulting residue purified by flash chromatography on 4 g of silica gel (0→20% gradient of MeOH in DCM)
  10. customThe pure fractions were collected
  11. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-9f5e33ebc0d246ff98f8daddf298b07d
Source dataset
uspto-grants-2010_03
Patent number
US07683176B2

Reaction notes

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