Triethylamine → HCID 19603645, compound

HRID 1604422Notes

Reaction equation

HRID 1604422 reaction equation
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][CH:10]=[C:9]3[CH2:15]C[CH2:17][OH:18])[CH:5]=1.[CH2:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH3:20].[CH3:26]S(Cl)(=O)=[O:28].[C:31](=[O:34])([O-:33])[O-].[K+].[K+].[C:37]1([CH:43](N2CCC=CC2)[CH3:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>O1CCCC1>[C:17]([OH:18])(=[O:28])[C:31]([OH:33])=[O:34].[C:37]1([CH:43]([C:44]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:15][C:9]3[C:8]4[C:12](=[CH:13][CH:14]=[C:6]([N:4]5[CH:5]=[N:1][N:2]=[CH:3]5)[CH:7]=4)[NH:11][CH:10]=3)[CH2:19][CH:20]=2)[CH3:26])[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 106339143-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-olHCID 20675357HCID 20675357, compound

Product 1

HCID 19603645HCID 19603645, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 3-(5-[1,2,4-triazol-4-yl]-1H-indol-3-yl)propan-1-ol (220 mg, 0.91 mmol) in anhydrous tetrahydrofuran (30 ml), under an atmosphere of nitrogen, was treated with triethylamine (0.25 ml, 1.82 mmol) and methanesulphonyl chloride (0.14 ml, 1.82 mmol). The reaction mixture was stirred for 1.5 hours, filtered, evaporated then re-dissolved in dichloromethane (50 ml) and washed with water (2×30 ml). The combined organics were dried (sodium sulphate), evaporated and the crude mesylate was suspended in propan-2-ol (50 ml) then treated with potassium carbonate (500 mg, 3.6 mmol) and 4-(1-phenylethyl-1,2,5,6-tetrahydropyridine (482 mg, 2.5 mmol). The reaction mixture was stirred whilst heating at reflux for 66 hours, then cooled and evaporated. The residue was partitioned between water (50 ml) and dichloromethane (50 ml). The aqueous was separated then re-extracted with dichloromethane (3×50 ml). The combined organics were dried (sodium sulphate), evaporated and the residue purified by chromatography on silica using dichloromethane/methanol/ammonia (95:4:1) to give the title compound free base (115 mg, 31%). The hydrogen oxalate salt had mp >120° C. (dec.). MS, ES+, m/z=412 for (M+H)+, δ(360 MHz, DMSO-d6) 1.31 (3H, d, J=7 Hz), 2.02-2.20 (4H, m), 2.78 (2H, t, J=7 Hz), 3.05-3.30 (4H, m), 3.45 (1H, q, J=7 Hz), 3.60-3.80 (2H, m), 5.56 (1H, s), 7.17-7.25 (3H, m), 7.27-7.35 (4H, m), 7.51 (1H, d, J=9 Hz), 7.80 (1H, d, J=2 Hz), 9.01 (2H, s), 11.20 (1H, s). (Found: C, 63,89; H, 6.23; N, 12.24. C26H29N5. 1.45C2H2O4. 0.33CH3CH2OH requires C, 63.71; H, 6.13; N, 12.57%).

Workup

  1. filtrationfiltered
  2. customevaporated
  3. dissolutionthen re-dissolved in dichloromethane (50 ml)
  4. washwashed with water (2×30 ml)
  5. dry with materialThe combined organics were dried (sodium sulphate)
  6. customevaporated
  7. stirringThe reaction mixture was stirred
  8. temperaturewhilst heating
  9. temperatureat reflux for 66 hours
  10. temperaturecooled
  11. customevaporated
  12. customThe residue was partitioned between water (50 ml) and dichloromethane (50 ml)
  13. customThe aqueous was separated
  14. extractionthen re-extracted with dichloromethane (3×50 ml)
  15. dry with materialThe combined organics were dried (sodium sulphate)
  16. customevaporated
  17. customthe residue purified by chromatography on silica

Sources & evidence

ORD record
ord-e15457f88348401eaee56f5db2ca66e3
Source dataset
uspto-grants-1999_11
Patent number
US05994374

Reaction notes

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