Hexylamine → HCID 49802508, compound

HRID 1677817Notes

Reaction equation

HRID 1677817 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 N HCl 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 N HCl 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-492227b135384b6ca0f9e657f070696d
Source dataset
uspto-grants-2011_08
Patent number
US08008341B2

Reaction notes

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