Sodium Iodide → HCID 18794752, compound

HRID 1004397Notes

Reaction equation

HRID 1004397 reaction equation
[N:1]1([CH2:6][C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][CH:11]=[C:10]3[CH2:16][CH2:17][CH2:18][OH:19])[CH:5]=[N:4][CH:3]=[N:2]1.C(N(CC)CC)C.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.[C:37](=[O:40])([O-:39])[O-].[I-].[Na+].[CH2:43]([C:50]1([O:56][CH3:57])[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1>[C:18]([OH:19])(=[O:56])[C:37]([OH:39])=[O:40].[CH2:43]([C:50]1([O:56][CH3:57])[CH2:55][CH2:54][N:53]([CH2:18][CH2:17][CH2:16][C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[C:7]([CH2:6][N:1]4[CH:5]=[N:4][CH:3]=[N:2]4)[CH:8]=3)[NH:12][CH:11]=2)[CH2:52][CH2:51]1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

9

Reactant 7

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 19660Carbonate IonHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 10729768HCID 10729768, compoundHCID 22730297HCID 22730297, compound

Product 1

HCID 18794752HCID 18794752, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A stirred, cooled (-5° C.) solution of 3-(5-[1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)propan-1-ol (260 mg, 1 mmol) in anhydrous tetrahydrofuran (20 ml), under a nitrogen atmosphere, was treated with triethylamine (0.17 ml, 1.2 mmol) and methanesulphonyl chloride (0.10 ml, 1.2 mmol). After 45 minutes the reaction mixture was filtered, then washed through the filter pad with tetrahydrofuran (10 ml). The resulting mesylate solution was treated with potssium carbonate (263 mg, 1.9 mmol), sodium iodide (285 mg, 1.9 mmol) and a solution of 4-benzyl-4-methoxypiperidine (400 mg, 1.9 mmol) in tetrahydrofuran (10 ml). The reaction mixture was stirred whilst heating at 50° C. for 24 hours. The solvent was evaporated, the residue partitioned between dichloromethane (40 ml) and water (20 ml). The organic layer was separated and the aqueous re-extracted with dichloromethane (40 ml). The combined organics were extracted with aqueous citric acid (1 g in 20 ml), the aqueous was basified to pH=12 with 40% aqueous soldium hydroxide then extracted with dichloromethane (3×30 ml). The organic extracts were combined, dried (potassium carbonate) then evaporated. The residue was purified by column chromatography on silica using dichloromethane/methanol/ammonia (9:1:0.1) to afford the title compound free base as a glass (332 mg, 75%). The hydrogen oxalate salt has mp 84°-87° C. (Found: C, 60.81: H. 6.34: N, 11.68. C27H33N5O. 1.75C2H2O4 requires C, 60.94; H, 6.12; N, 11.65%). δH (360 MHz, DMSO-d6) 1.6-5-1.78 (2H, m, 2×CH), 1.82 (2H, d, J=12 Hz, 2×CH), 1.94-2.04 (2H, m, CH2CH2CH2), 2.71 (2H, t, J=7 Hz, indole-CH2), 2.82 (2H, s, CH2Ph), 2.82-3.00 (2H, m, 2×CH), 3.02-3.12 (2H, m, CH2N), 3.22-3.32 (2H, m, 2×CH), 3.28 (3H, s, OCH3) 5.43 (2H, s, CH2 -triazole), 7.05 (1H, d, J=7 Hz, Ar-H), 7.18-7.34 (7H, m, C6H5, indole-H, Ar-H), 7.52 (1H, s, Ar-H), 7.94 (1H, s, triazole-H), 8.60 (1H, s, triazole-H), 10.92 (1H, s, indole-NH); m/z (ES) 444 (M+ +1).

Workup

  1. filtrationAfter 45 minutes the reaction mixture was filtered
  2. washwashed through the filter pad with tetrahydrofuran (10 ml)
  3. customThe solvent was evaporated
  4. customthe residue partitioned between dichloromethane (40 ml) and water (20 ml)
  5. customThe organic layer was separated
  6. extractionthe aqueous re-extracted with dichloromethane (40 ml)
  7. extractionThe combined organics were extracted with aqueous citric acid (1 g in 20 ml)
  8. extractionthen extracted with dichloromethane (3×30 ml)
  9. dry with materialdried (potassium carbonate)
  10. customthen evaporated
  11. customThe residue was purified by column chromatography on silica

Sources & evidence

ORD record
ord-aefb0d3ef117401e9ccf9133a78a8f54
Source dataset
uspto-grants-2000_04
Patent number
US06048878

Reaction notes

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