Cyclohexylamine → N-cy clohexyl-1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxamide

HRID 2385525Notes

Reaction equation

HRID 2385525 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]([OH:13])=O)[C:5]=2[C:4]2([C:25]3[C:16](=[CH:17][C:18]4[O:23][CH2:22][CH2:21][O:20][C:19]=4[CH:24]=3)[O:15][CH2:14]2)[C:3]1=[O:26].C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.O[C:48]1[C:56]2N=N[NH:53][C:52]=2[CH:51]=[CH:50][CH:49]=1.C1(N)CCCCC1>CN(C)C=O>[CH:52]1([NH:53][C:11]([C:6]2[C:5]3[C:4]4([C:25]5[C:16](=[CH:17][C:18]6[O:23][CH2:22][CH2:21][O:20][C:19]=6[CH:24]=5)[O:15][CH2:14]4)[C:3](=[O:26])[N:2]([CH3:1])[C:10]=3[CH:9]=[CH:8][CH:7]=2)=[O:13])[CH2:56][CH2:48][CH2:49][CH2:50][CH2:51]1

Participants

7

Reactant 5

HCID 7965CyclohexylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 593522691'-Methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 59352661N-cy clohexyl-1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxamideYield 51.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1′-methyl-2′-oxo-1,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxylic acid (0.200 g, 0.566 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (0.114 g, 0.736 mmol) in N,N-dimethylformamide (20 mL) was added N,N-diisoproylethylamine (0.30 mL, 1.72 mmol) and hydroxybenzotriazole (0.092 g, 0.68 mmol). The reaction mixture was stirred at ambient temperature for 10 min and cyclohexylamine (0.10 mL, 0.87 mmol) was added. The reaction mixture was stirred at ambient temperature for 40 h and concentrated in vacuo to remove most of the N,N-dimethylformamide. The mixture was diluted with ethyl acetate (150 mL), washed with water (3×150 mL) and brine (3×100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate/hexanes (1/1) to afford N-cyclohexyl-1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide (0.127 g, 51%) as a colorless solid: mp 139-140° C.; 1H NMR (300 MHz, CDCl3) δ7.42-7.36 (m, 1H), 7.24-7.20 (m, 1H), 6.98-6.94 (m, 1H), 6.51 (s, 1H), 6.17 (s, 1H), 5.30-5.27 (m, 1H), 4.95 (ABq, 2H), 4.24-4.04 (m, 4H), 3.71-3.61 (m, 1H), 3.26 (s, 3H), 1.78-1.57 (m, 5H), 1.36-1.22 (m, 2H), 1.12-0.99 (m, 1H), 0.89-0.82 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.6, 166.3, 155.9, 145.0, 144.3, 137.9. 134.7, 129.5, 127.4, 122.8, 120.4, 110.7, 109.9, 100.1. 78.0, 64.5, 64.0, 58.2, 48.7, 32.4, 32.1, 26.7, 25.5, 24.9, 24.7; MS (ES+) m/z 435.0 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 40 h
  2. concentrationconcentrated in vacuo
  3. customto remove most of the N,N-dimethylformamide
  4. additionThe mixture was diluted with ethyl acetate (150 mL)
  5. washwashed with water (3×150 mL) and brine (3×100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography
  10. washeluted with ethyl acetate/hexanes (1/1)

Sources & evidence

ORD record
ord-227ed47b0e394270a3769c88179e52e0
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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