Sodium Iodide → (S)-3-((R)-9-azido-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxyisobenzofuran-1(3H)-one

HRID 2408263Notes

Reaction equation

HRID 2408263 reaction equation
Br[C:2]1[C:3]2[CH2:4][CH2:5][N:6]([CH3:31])[C@@H:7]([C@@H:17]3[C:25]4[C:20](=[C:21]([O:28][CH3:29])[C:22]([O:26][CH3:27])=[CH:23][CH:24]=4)[C:19](=[O:30])[O:18]3)[C:8]=2[C:9]([O:15][CH3:16])=[C:10]2[O:14][CH2:13][O:12][C:11]=12.[N-:32]=[N+:33]=[N-:34].[Na+].[I-].[Na+]>CN(C=O)C>[N:32]([C:2]1[C:3]2[CH2:4][CH2:5][N:6]([CH3:31])[C@@H:7]([C@@H:17]3[C:25]4[C:20](=[C:21]([O:28][CH3:29])[C:22]([O:26][CH3:27])=[CH:23][CH:24]=4)[C:19](=[O:30])[O:18]3)[C:8]=2[C:9]([O:15][CH3:16])=[C:10]2[O:14][CH2:13][O:12][C:11]=12)=[N+:33]=[N-:34]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 33557Sodium AzideHCID 102550819-Bromonoscapine

Product 1

HCID 86659030(S)-3-((R)-9-azido-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxyisobenzofuran-1(3H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of compound 2 (2.0 g, 4.063 mmol) in DMF (20 mL) were added sodium azide (2.641 g, 40.63 mmol) and sodium iodide (0.609 g, 4.063 mmol) and the reaction mixture was stirred at 80° C. for 15 h to attain completion. Then the solvent was removed in vacuo and the resultant residue was dissolved in chlorofrom (40 mL), washed with water (2×40 mL), dried over sodium sulfate and concentrated to obtain the titled compound 3, which was recrystallized with ethanol in hexane (10:90) to afford brown crystals. Yield, 89%; mp 177.2-178.1° C.; IR: 1529, 1362 cm−1; 1H NMR (CDCl3, 400 MHz): δ 7.05 (d, 1H, J=7.0 Hz), 6.4 (d, 1H, J=7.0 Hz), 6.01 (s, 2H), 5.85 (d, 1H, J=4.4 Hz), 4.40 (d, 1H, J=4.4 Hz), 4.15 (s, 3H), 3.88 (s, 3H), 3.84 (s, 3H), 2.75-2.62 (m, 2H), 2.60-2.56 (m, 2H), 2.51 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 169.2, 157.7, 152.6, 147.9, 142.2, 140.5, 135.0, 134.0, 123.5, 121.8, 119.7, 119.3, 114.1, 100.5, 87.4, 64.1, 56.7, 56.5, 56.2, 51.4, 39.2, 27.2; HRMS (ESI): m/z Calcd. for C22H23N4O7 (M+1), 455.4335; Found, 455.4452 (M+1).

Workup

  1. customThen the solvent was removed in vacuo
  2. dissolutionthe resultant residue was dissolved in chlorofrom (40 mL)
  3. washwashed with water (2×40 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-064539f3a7b84660bfe9057a17409775
Source dataset
uspto-grants-2014_08
Patent number
US08815835B2

Reaction notes

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