Sodium Iodide → N-[1-[3-(4-tert-butoxycarbonylaminophenyl)propan-1-yl]piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide

HRID 1978541Notes

Reaction equation

HRID 1978541 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:11][CH:10]=1)(=O)=O.Cl.Cl.[NH:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:32]([C:34]2[S:44][C:43]3[N:45]4[C:36](=[CH:37][N:38]=[C:39]4[CH:40]=[CH:41][CH:42]=3)[CH:35]=2)=[O:33])[CH2:27][CH2:26]1.C(N(CC)CC)C.[I-].[Na+].N12CCCNC1CCCC=C2>C(#N)C>[C:19]([O:18][C:16]([NH:15][C:12]1[CH:11]=[CH:10][C:9]([CH2:8][CH2:7][CH2:6][N:25]2[CH2:26][CH2:27][CH:28]([NH:31][C:32]([C:34]3[S:44][C:43]4[N:45]5[C:36](=[CH:37][N:38]=[C:39]5[CH:40]=[CH:41][CH:42]=4)[CH:35]=3)=[O:33])[CH2:29][CH2:30]2)=[CH:14][CH:13]=1)=[O:17])([CH3:20])([CH3:21])[CH3:22]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 98128211,8-Diazabicyclo[5.4.0]undec-2-eneHCID 219936273-{4-[(Tert-butoxycarbonyl)amino]phenyl}propyl methanesulfonateHCID 21994154N-(piperidin-4-yl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride

Product 1

HCID 21994165N-[1-[3-(4-tert-butoxycarbonylaminophenyl)propan-1-yl]piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamideYield 61.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-(4-tert-Butoxycarbonylaminophenyl)propyl methanesulfonate (423 mg, 1.28 mmol) was added to a stirred solution of N-(piperidin-4-yl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride (400 mg, 1.07 mmol), triethylamine (539 mg, 5.33 mmol), sodium iodide (192 mg, 1.28 mmol) and 1,8-diazabicyclo[5.4.0]undecene (326 mg, 2.14 mmol) in acetonitrile (20 ml) at room temperature. After refluxing under nitrogen for 1 day, the reaction mixture was concentrated in vacuo. The residue was dissolved in water and extracted with chloroform. The extract was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed on silica gel (20 g) with Ethyl acetate-Methanol (3:1) to give N-[1-[3-(4-tert-butoxycarbonylaminophenyl)propan-1-yl]piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide as purple amorphous powder (350 mg, 61%).

Workup

  1. temperatureAfter refluxing under nitrogen for 1 day
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in water
  4. extractionextracted with chloroform
  5. washThe extract was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed on silica gel (20 g) with Ethyl acetate-Methanol (3:1)

Sources & evidence

ORD record
ord-49960585fa944afc8319cfb47b5248b0
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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