Hydrochloric Acid → N-(2-(2-(4-Hydroxy-4-(pyridin-3-ylmethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide hydrochloride

HRID 2041098Notes

Reaction equation

HRID 2041098 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH2:15][CH2:16][O:17][CH2:18][C:19]([OH:21])=O)[CH3:14])(=[O:12])=[O:11])=[C:5]([CH3:22])[CH:4]=1.[ClH:23].Cl.[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][C:32]2([OH:38])[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:26]=1.C(=O)(O)[O-].[Na+].Cl.CCOCC.N1C=CC=C(C2(O)CCNCC2)C=1.N1C=CC(C2(O)CCNCC2)=CC=1.S1C=CC=C1C1(O)CCNCC1.N1CCCCC1=O>C(Cl)Cl.C(N(CC)CC)C>[ClH:23].[OH:38][C:32]1([CH2:31][C:27]2[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=2)[CH2:37][CH2:36][N:35]([C:19](=[O:21])[CH2:18][O:17][CH2:16][CH2:15][N:13]([CH3:14])[S:10]([C:6]2[C:5]([CH3:22])=[CH:4][C:3]([O:2][CH3:1])=[CH:8][C:7]=2[CH3:9])(=[O:11])=[O:12])[CH2:34][CH2:33]1

Participants

12

Reactant 9

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 126652-PiperidoneHCID 516892Sodium BicarbonateHCID 37269594-(4-Pyridinyl)-4-piperidinolHCID 49891674-(Pyridin-3-yl)piperidin-4-olHCID 14441129HCID 14441129, compoundHCID 46870354{2-[(4-methoxy-2,6-dimethyl-benzenesulfonyl)-methyl-amino]-ethoxy}acetic AcidHCID 688011574-(Pyridin-3-ylmethyl)piperidin-4-ol dihydrochloride

Product 1

HCID 69321929N-(2-(2-(4-Hydroxy-4-(pyridin-3-ylmethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide hydrochloride

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

N,N′-Carbonyldiimidazole (77 mg, 0.475 mmol) was added to a solution of 2-(2-(4-methoxy-N,2,6-trimethylphenylsulfonamido)-ethoxy)acetic acid (acid unit S2) (150 mg, 0.453 mmol) in methylene chloride (7 ml), and the mixture was stirred for 1 h at room temperature. A solution of 4-(pyridin-3-ylmethyl)piperidin-4-ol dihydrochloride (120 mg, 0.453 mmol) dissolved in methylene chloride (3 ml) and triethylamine (0.18 ml) was then added, and the reaction mixture was stirred overnight at room temperature. Saturated sodium bicarbonate solution (10 ml) was then added to the reaction mixture, and the aqueous phase was then extracted with methylene chloride (20 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried with sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography with ether/methylene chloride/methanol (10:10:1) and 25% strength ammonia solution. N-(2-(2-(4-Hydroxy-4-(pyridin-3-ylmethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide (140 mg) was dissolved in methyl ethyl ketone (1 ml), and HCl in ether (3 eq.) was added slowly, whereupon a white solid precipitated. After addition of diethyl ether, stirring was carried out for 1 h, while cooling with ice. The solid was filtered off, washed with diethyl ether and dried. Yield: 120 mg (48%). The amine units used in Examples 279 and 280 can be prepared analogously to the synthesis processes described above for amine units A2, A3, A4 and A7 with addition of a corresponding Li organyl or Grignard radical to the corresponding piperidone derivative.

Workup

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. extractionthe aqueous phase was then extracted with methylene chloride (20 ml)
  3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (10 ml)
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography with ether/methylene chloride/methanol (10:10:1) and 25% strength ammonia solution
  7. dissolutionN-(2-(2-(4-Hydroxy-4-(pyridin-3-ylmethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide (140 mg) was dissolved in methyl ethyl ketone (1 ml)
  8. customprecipitated
  9. additionAfter addition of diethyl ether
  10. stirringstirring
  11. waitwas carried out for 1 h
  12. temperaturewhile cooling with ice
  13. filtrationThe solid was filtered off
  14. washwashed with diethyl ether
  15. customdried
  16. customcan be prepared analogously to the synthesis processes

Sources & evidence

ORD record
ord-8e2a93d3119a45fc8b402734e1ae99e9
Source dataset
uspto-grants-2013_11
Patent number
US08580965B2

Reaction notes

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