Triethylamine → HCID 11758087, compound

HRID 860173Notes

Reaction equation

HRID 860173 reaction equation
[Br:1][C:2]1[S:6][C:5]([S:7]([Cl:10])(=[O:9])=[O:8])=[CH:4][CH:3]=1.[CH2:11]([N:13]1[C:17]([CH:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH:26]([NH2:33])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:20][CH2:19]2)=[CH:16][C:15]([CH3:34])=[N:14]1)[CH3:12].CCN(CC)CC>C(Cl)Cl>[ClH:10].[CH2:11]([N:13]1[C:17]([CH:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH:26]([NH:33][S:7]([C:5]3[S:6][C:2]([Br:1])=[CH:3][CH:4]=3)(=[O:9])=[O:8])[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:20][CH2:19]2)=[CH:16][C:15]([CH3:34])=[N:14]1)[CH3:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27339245-Bromothiophene-2-sulfonyl chlorideHCID 69446259HCID 69446259, compound

Product 1

HCID 11758087HCID 11758087, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(5-Bromothien-2-yl)sulfonylchloride (34 mg, 0.13 mmol) was added dropwise to a stirred solution of 3-[4-(2-ethyl-5-methyl-2H-pyrazol-3-yl)-piperidin-1-yl]-1-phenyl-propylamine (see Example 8 (48 mg, 0.15 mmol) and Et3N (20 μL, 0.14 mmol) in CH2Cl2 (2 mL) at RT under N2 and the mixture was stirred for 3 hours. The solution was diluted with CH2Cl2 (20 mL) and then washed with NaHCO3 solution (20 mL), and the organic layer separated. The aqueous phase was re-extracted with CH2Cl2 (20 mL) and the combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography on silica using 5% MeOH/CH2Cl2 as eluent. The fractions containing the desired product were combined and concentrated under reduced pressure. The residue was taken up in Et2O (5 mL) and a solution of HCl in Et2O was added. The resultant solid was purified by trituration to isolate the title compound (8 mg, 10%) as a colourless solid. 1H NMR (d6-DMSO, 400 MHz) δ 10.32 (1H, s), 8.85 (1H, d, J=9.1 Hz), 7.24–7.19 (5H, m), 7.09 (1H, d, J=4.0 Hz), 7.06 (1H, d, J=4.0 Hz), 5.80 (1H, s), 4.46–4.40 (1H, m), 3.99 (2H, q, J=7.2 Hz), 3.51–3.41 (2H, m), 3.15–2.87 (5H, m), 2.42–2.00 (5H, m), 1.98–1.80 (4H, m), 1.28 (3H, t, J=7.2 Hz). MS (ES+) C24H31BrN4O2S2 requires: 550, found: 551/553 (1:1, M+H+).

Workup

  1. customat RT
  2. washwashed with NaHCO3 solution (20 mL)
  3. customthe organic layer separated
  4. extractionThe aqueous phase was re-extracted with CH2Cl2 (20 mL)
  5. dry with materialthe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica using 5% MeOH/CH2Cl2 as eluent
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated under reduced pressure
  10. additiona solution of HCl in Et2O was added
  11. customThe resultant solid was purified by trituration

Sources & evidence

ORD record
ord-5d9ebb3a629e43c6852a4937db337c83
Source dataset
uspto-grants-2006_12
Patent number
US07153868B2

Reaction notes

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