Diisopropylethylamine → Hydrochloric Acid

HRID 416489Notes

Reaction equation

HRID 416489 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:43]([N:46]1[CH2:51][CH2:50][CH:49]([NH:52][S:53]([CH2:56][CH2:57][NH2:58])(=[O:55])=[O:54])[CH2:48][CH2:47]1)([CH3:45])[CH3:44]>CN(C=O)C>[ClH:1].[CH:43]([N:46]1[CH2:51][CH2:50][CH:49]([NH:52][S:53]([CH2:56][CH2:57][NH:58][C:7]([C:5]2[S:6][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:9])(=[O:54])=[O:55])[CH2:48][CH2:47]1)([CH3:45])[CH3:44]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 950485-Chloro-2-thiophenecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666246312-Amino-ethanesulfonic acid (1-isopropyl-piperidin-4-yl)-amide

Product 2

HCID 313Hydrochloric AcidHCID 119904785-Chloro-Thiophene-2-Carboxylic Acid [2-(1--Isopropyl-Piperidin-4-Ylsulfamoyl)-Ethyl]-Amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1.87 g (1.75 equiv.) 5-chloro-thiophene-2-carboxylic acid in 50 ml DMF were added 4.39 g (1.75 equiv.) HATU and 3.35 ml (3 equiv.) DIPEA. The resulting mixture was stirred for 30 min at room temperature. Subsequently a solution of 1.64 g (6.58 mmol) 2-amino-ethanesulfonic acid (1-isopropyl-piperidin-4-yl)-amide and 1.11 ml (1 equiv.) DIPEA in 20 ml DMF was added. The resulting mixture was stirred at room temperature overnight and concentrated under reduced pressure. The resulting residue was taken up in ethyl acetate and filtered. The filtrate was washed with a saturated NaHCO3-solution. Then, the product was extracted into the aqueous phase by treatment with a 0.1 N HCl-solution. Separation of the aqueous phase, then adjusting the pH to ≈9 by treatment with a saturated NaHCO3-solution and subsequent re-extraction with ethyl acetate brought the product back in the organic phase. Concentration under reduced pressure afforded crude 5-chloro-thiophene-2-carboxylic acid [2-(1-isopropyl-piperidin-4-ylsulfamoyl)-ethyl]-amide. Final purification was achieved by preparative RP-HPLC (CH3CN/H2O gradient+0.1% TFA). Lyophilisation and transformation into its hydrochloride gave the title compound as a colorless, amorphous solid. Yield: 1.76 g MS (ES+): m/e=394, chloro pattern.

Workup

  1. stirringThe resulting mixture was stirred at room temperature overnight
  2. concentrationconcentrated under reduced pressure
  3. filtrationfiltered
  4. washThe filtrate was washed with a saturated NaHCO3-solution
  5. extractionThen, the product was extracted into the aqueous phase by treatment with a 0.1 N HCl-solution
  6. customSeparation of the aqueous phase
  7. extractionwith a saturated NaHCO3-solution and subsequent re-extraction with ethyl acetate
  8. concentrationConcentration under reduced pressure
  9. customafforded crude 5-chloro-thiophene-2-carboxylic acid [2-(1-isopropyl-piperidin-4-ylsulfamoyl)-ethyl]-amide
  10. customFinal purification

Sources & evidence

ORD record
ord-f9b2bd3b515849ef83f9c9cf4d30f976
Source dataset
uspto-grants-2012_01
Patent number
US08088925B2

Reaction notes

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