Methanesulfonic Acid → HCID 178477846, compound

HRID 1634579Notes

Reaction equation

HRID 1634579 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:15]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:22]=1.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:30]2[CH:34]=[C:33]([CH:35]([CH2:38][CH2:39][CH3:40])C=O)[N:32]=[CH:31]2)C=CC=CC=1.[CH3:53]S(O)(=O)=O.S([O-])([O-])(=O)=O.[Mg+2].C([BH3-])#N.[Na+].O1CCCC1>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:15]([CH:16]3[CH2:17][CH2:18][N:19]([CH2:53][CH2:40][CH2:39][CH2:38][CH2:35][C:33]4[N:32]=[CH:31][NH:30][CH:34]=4)[CH2:20][CH2:21]3)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:22]=1

Participants

8

Reactant 6

HCID 6395Methanesulfonic AcidHCID 8028TetrahydrofuranHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5003444Sodium cyanoborohydrideHCID 10495356HCID 10495356, compoundHCID 86585406HCID 86585406, compound

Product 1

HCID 178477846HCID 178477846, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 8-Chloro-6,11-dihydro-11-(4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (9) (499 mg; 1.59 mmol) (disclosed in published application WO 95/10516, Apr. 20, 1995), ω-[1-(triphenylmethyl)-1H-imidazol-4-yl]-pentanal (6) (699 mg; ˜90% pure; 1.59 mmol) and methanesulfonic acid (0.10 mL; 1.59 mmol)) in anhydrous methanol (100 mL), was added anhydrous magnesium sulfate (380 mg) The resultant suspension was stirred at room temperature for 45 min. A 1.0M solution of sodium cyanoborohydride in tetrahydrofuran (1.12 mL; 1.12 mmol) was added and the resultant mixture stirred at room temperature for 22 h. The reaction mixture was filtered through Celite, and solvent evaporated under reduced pressure. The residue was dissolved in dichloromethane (25 mL) and washed successively with 1.1M sodium bicarbonate (15 mL) and water (2×10 mL). The organic layers were dried over anhydrous magnesium sulfate; filtered; solvent evaporated under reduced pressure and dried under high vacuum to obtain a pink glassy solid. The residual solid was chromatographed on silica gel, eluting with a gradient of 3.9M ammonia in methanol-dichloromethane (3:97→5:95), to obtain the imidazole-N-tritylated precursor of the title compound, which, after drying under high vacuum, was an off-white foam, mp 75-78° C. (melted to a viscous gum). FABMS: 451 (MH+; 20%); 243 (Ph3C+; 100%).

Workup

  1. filtrationThe reaction mixture was filtered through Celite, and solvent
  2. customevaporated under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane (25 mL)
  4. washwashed successively with 1.1M sodium bicarbonate (15 mL) and water (2×10 mL)
  5. dry with materialThe organic layers were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customsolvent evaporated under reduced pressure
  8. customdried under high vacuum
  9. customto obtain a pink glassy solid
  10. customThe residual solid was chromatographed on silica gel
  11. washeluting with a gradient of 3.9M ammonia in methanol-dichloromethane (3:97→5:95)

Sources & evidence

ORD record
ord-f11ec5a8e63141aaba76660aea090f96
Source dataset
uspto-grants-2003_01
Patent number
US06506756B2

Reaction notes

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