Hexylamine → HCID 49802508, compound

HRID 2220157Notes

Reaction equation

HRID 2220157 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([N:19]3[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]3)(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[O:7])=[CH:4][CH:3]=1.[CH2:28]([NH2:34])[CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>C1COCC1.CO>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([N:19]3[CH2:24][CH2:23][CH:22]([NH:34][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:21][CH2:20]3)(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[O:7])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 8102HexylamineHCID 86591407HCID 86591407, compound

Product 1

HCID 49802508HCID 49802508, compound

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

4-chloro-N-{4-[(4-oxo-1-piperidinyl)sulfonyl]benzyl}benzamide 7d (500 mg, 1.23 mmol) was suspended in THF/methanol (10 ml/20 ml), N-hexylamine (149 mg, 1.48 mmol) and Cyanoborohydride-IRA400 (1.0 g, 3.0 mmol) were added and the reaction mixture was stirred at 50° C. overnight. Excess amine was scavenged with Ameba-PS (415 mg, 0.50 mmol) by shaking for 2 h. The resins were filtered off, solvent removed in vacuo and the obtained residue purified by column chromatography on silica gel using a step gradient of 2.5% methanol in DCM and 5% methanol in DCM. Fractions with Rf=0.28 (5% methanol in DCM, ) were collected and evaporated to dryness (Note: Up to 1% conc. NH3 (13.5 M) may be added during the chromatography to reduce loss of material). The residue was dissolved in DCM (10 ml) and 1 NHCl in ether (3 ml) added. After aging at room temp for 1 h the precipitate was filtered off and dried in vacuo. The hydrochloric salt of sulfonamide 4-chloro-N-(4-{[4-(hexylamino)-1-piperidinyl]sulfonyl}benzyl)benzamide 7 was isolated as off-white powder (260 mg, 36%) in >95% purity. M/Z APCI 492.0 (M+1), 490.2 (M−1). 1H-NMR (DMSO-d6) (HCl salt) δ 9.39 (t, 1H, H-N5, 3J=5.92 Hz), 8.97 (m, br, 2H, H-N16), 7.99 (d, 2H, 3J=8.65 Hz, H-C2,3), 7.75 (d, 2H, 3J=8.20 Hz, H-C8,9), 7.61 (m, 4H, H-C1,4,7,10), 4.61 (d, 2H, 3J=5.92 Hz, H-C6), 3.73* (d, 2H, 2J=11.84 Hz, Heq-C11,15), 3.07 (m, br, 1H, H-C13), 2.83 (m, br, 2H, H-C17), 2.29* (m, 2H, Hax-C12,14), 2.10* (d, br, 2H, 2J=11.90 Hz, Hax-C11,15), 1.71-1.54* (m, 4H, Heq-C12,14 and H-C18), 1.36-1.23 (m, 6H, H-C19,20,21), 0.89 (t, 3H, 3J=6.60 Hz, H-C22)

Workup

  1. stirringby shaking for 2 h
  2. filtrationThe resins were filtered off
  3. customsolvent removed in vacuo
  4. customthe obtained residue purified by column chromatography on silica gel using a step gradient of 2.5% methanol in DCM and 5% methanol in DCM
  5. customFractions with Rf=0.28 (5% methanol in DCM, ) were collected
  6. customevaporated to dryness (Note
  7. additionUp to 1% conc. NH3 (13.5 M) may be added during the chromatography
  8. dissolutionThe residue was dissolved in DCM (10 ml)
  9. addition1 NHCl in ether (3 ml) added
  10. waitAfter aging at room temp for 1 h
  11. filtrationthe precipitate was filtered off
  12. customdried in vacuo

Sources & evidence

ORD record
ord-8510f39a1bea46319cc009b7039c4a13
Source dataset
uspto-grants-2008_08
Patent number
US07417058B2

Reaction notes

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