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

HRID 1965775Notes

Reaction equation

HRID 1965775 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].O[C:28]1[C:36]2N=N[NH:33][C:32]=2[CH:31]=[CH:30][CH:29]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.C(N)CCCCC>CN(C)C=O>[CH2:32]([NH:33][C:11]([C:6]1[C:5]2[C:4]3([C:25]4[C:16](=[CH:17][C:18]5[O:23][CH2:22][CH2:21][O:20][C:19]=5[CH:24]=4)[O:15][CH2:14]3)[C:3](=[O:26])[N:2]([CH3:1])[C:10]=2[CH:9]=[CH:8][CH:7]=1)=[O:13])[CH2:31][CH2:30][CH2:29][CH2:28][CH3:36]

Participants

7

Reactant 5

HCID 8102HexylamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 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 59352330N-hexyl-1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxamideYield 73%

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) in N,N-dimethylformamide (12 mL) were added hydroxybenzotriazole (0.151 g, 1.13 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.364 g, 1.13 mmol) and N,N-diisopropylethylamine (0.81 mL, 4.5 mmol). The reaction mixture was stirred at ambient temperature for 15 min and N-hexylamine (0.15 mL, 1.1 mmol) was added. The reaction mixture stirred for 72 h at ambient temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate and was washed with water (3×150 mL), 1 M aqueous sodium hydroxide (2×100 mL) and brine (2×100 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was recrystallized from hexanes/ethyl acetate to afford N-hexyl-1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide (0.180 g, 73%) as a colorless solid: mp 172-173° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 7.42-7.36 (m 1H), 7.26-7.22 (m, 1H), 6.99-6.96 (m, 1H), 6.49 (s, 1H), 6.20 (s, 1H), 5.30-5.26 (m, 1H), 4.92 (ABq, 2H), 4.25-4.07 (m, 4H), 3.27-2.97 (m, 5H), 1.30-1.18 (m, 8H), 0.87 (t, J=6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 177.6, 167.0, 155.8, 145.0, 144.1, 137.9, 134.4, 129.5, 127.8, 122.9, 120.6, 110.7, 109.9, 99.8, 78.8, 64.5, 64.0, 58.1, 40.0, 31.4, 28.9, 26.9, 26.5, 22.5, 14.0; MS (ES+) m/z 437.1 (M+1).

Workup

  1. stirringThe reaction mixture stirred for 72 h at ambient temperature
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwas washed with water (3×150 mL), 1 M aqueous sodium hydroxide (2×100 mL) and brine (2×100 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was recrystallized from hexanes/ethyl acetate

Sources & evidence

ORD record
ord-ac0fa6fcb66f4f14a2b4a923c6c53816
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

Loading…