Hydrochloric Acid → HCID 68581169, compound

HRID 2234005Notes

Reaction equation

HRID 2234005 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:23](O)=[O:24])=[CH:21][N:22]=2)[CH2:14][CH2:13]1)=[O:10].S(Cl)(Cl)=O.[CH3:30][S:31]([NH2:34])(=[O:33])=[O:32].C1CCN2C(=NCCC2)CC1.Cl>C1(C)C=CC=CC=1.O1CCOCC1>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][CH:12]1[CH2:13][CH2:14][N:15]([C:18]2[S:19][C:20]([C:23]([NH:34][S:31]([CH3:30])(=[O:33])=[O:32])=[O:24])=[CH:21][N:22]=2)[CH2:16][CH2:17]1)=[O:10]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 11463807HCID 11463807, compound

Product 1

HCID 68581169HCID 68581169, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

2-(4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-1,3-thiazole-5-carboxylic acid (Example 227; 0.160 g, 0.397 mmol) was suspended in toluene (3 ml) and thionyl chloride (0.288 ml, 3.97 mmol) was added dropwise at room temperature. The solution was refluxed for 1 h. Excess thionyl chloride and toluene were removed in vacuo. The precipitate formed was dissolved in dioxane and methane sulfonamide (0.075 g, 0.794 mmol) was added. The mixture was stirred at 100° C. for 0.5 h after which DBU (0.119 ml, 0.794 mmol) was added. The mixture was stirred for a further 1 h at room temperature was acidified with 10% HCl solution. The mixture was extracted with EtOAc and washed with water. The organic layer was dried over sodium sulfate and conc in vacuo. The crude mixture dissolved in DMSO, and was purified by reverse phase HPLC eluting with acetonitrile/water (0.1% TFA) to afford the desired product. (15 mg).

Workup

  1. temperatureThe solution was refluxed for 1 h
  2. customExcess thionyl chloride and toluene were removed in vacuo
  3. customThe precipitate formed
  4. additionwas added
  5. extractionThe mixture was extracted with EtOAc
  6. washwashed with water
  7. dry with materialThe organic layer was dried over sodium sulfate and conc in vacuo
  8. dissolutionThe crude mixture dissolved in DMSO
  9. customwas purified by reverse phase HPLC
  10. washeluting with acetonitrile/water (0.1% TFA)

Sources & evidence

ORD record
ord-18ef67326a644ab9b5aeb20f6da261b6
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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