Hydrochloric Acid → 4-(3-Cyclopentyl-indole-1-sulfonyl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamide

HRID 737048Notes

Reaction equation

HRID 737048 reaction equation
[CH:1]1([C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]([S:15]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=3)(=[O:17])=[O:16])[CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.[NH2:45][CH2:46][CH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1.Cl>C1COCC1.C(Cl)Cl>[CH:1]1([C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]([S:15]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([NH:45][CH2:46][CH:47]4[CH2:52][CH2:51][O:50][CH2:49][CH2:48]4)=[O:24])=[CH:20][CH:19]=3)(=[O:16])=[O:17])[CH:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 27732104-AminomethyltetrahydropyranHCID 58975136HCID 58975136, compound

Product 1

HCID 112021584-(3-Cyclopentyl-indole-1-sulfonyl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

Stir a stir solution of 4-(3-cyclopentyl-indole-1-sulfonyl)-benzoic acid (19.0 g, 51.43 mmol) in anhydrous THF (250 mL) cool to 5° C. under N2 add N-methylmorpholine (5.8 mL, 52.72 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (9.0 g, 51.34 mmol). Stir the mixture for 1 h and add a solution of 4-aminomethyltetrahydropyran (6.6 g, 57.34 mmol) in dry THF (75 mL) by dropping funnel. Warm the mixture to room temperature and stir for 3 h. Cool the mixture to 5° C., add 1N HCl (250 mL) and partition the resulting solution with ethyl acetate (250 mL). Extract the organic layer with aqueous saturated sodium bicarbonate (250 mL), brine (250 mL), and dry over sodium sulfate. Concentrate to give a foam, dissolve in minimum methylene chloride and add to a flash 65 M cartridge. Elute with 3:2 hexanes/ethyl acetate to give the major product as a solid, filter from hexanes, and dry (20 mm Hg, 40° C.) to give the homogeneous white solid (20.5 g, 85%); MS (ESI) m/z 467 (m+H).

Workup

  1. temperatureWarm the mixture to room temperature
  2. stirringstir for 3 h
  3. temperatureCool the mixture to 5° C.
  4. custompartition the resulting solution with ethyl acetate (250 mL)
  5. extractionExtract the organic layer with aqueous saturated sodium bicarbonate (250 mL), brine (250 mL)
  6. dry with materialdry over sodium sulfate
  7. concentrationConcentrate
  8. customto give a foam
  9. additionadd to a flash 65 M cartridge
  10. washElute with 3:2 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-9308f3f7aa474b81a8674b5fa7501877
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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