Thionyl Chloride → HCID 67368039, compound

HRID 1877359Notes

Reaction equation

HRID 1877359 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[N:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.S(Cl)(Cl)=O.C(N(C(C)C)C(C)C)C.[CH3:32][CH:33]1[CH2:42][CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[NH:34]1>>[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[C:6]([C:7]([N:34]2[C:35]3[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:41][CH2:42][CH:33]2[CH3:32])=[O:9])=[CH:10][CH:11]=[CH:12][N:13]=1

Participants

5

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 962892-Methyl-1,2,3,4-tetrahydroquinolineHCID 167959962-(2,5-Dichloro-phenoxy)-nicotinic acid

Product 1

HCID 67368039HCID 67368039, compoundYield 18.1%

Conditions

Temperature
100 °C

Procedure

A solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (34.1 mg, 0.12 mmol, 1.0 equiv; Example 31, Step 1) in thionyl chloride (492 mg, 300 μL, 4.14 mmol, 34.5 equiv; [CAS RN 7719-09-7]) was heated to 100° C. over night. The reaction mixture was concentrated under reduced pressure, remaining thionyl chloride removed by azotropic distillation with toluene and the residue dissolved in anhydrous DMF (1 mL). To this solution was added N-ethyldiisopropylamine (155 mg, 204 μL, 1.20 mmol, 10.0 equiv; [CAS RN 7087-68-5]) and 2-methyl-1,2,3,4-tetrahydro-quinoline (22.1 mg, 0.15 mmol, 1.25 equiv; [CAS RN 1780-19-4]) and the reaction mixture heated by microwave irradiation to 100° C. for 15 min. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 9 mg (18%) of the title compound. MS (ISP): 412.9 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customremoved by azotropic distillation with toluene
  3. dissolutionthe residue dissolved in anhydrous DMF (1 mL)
  4. customRemoval of the solvent mixture
  5. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  6. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  7. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-fb0b4481b754456995b2ab9e5c1e1a9e
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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