Sodium Iodide → HCID 86693510, compound

HRID 575448Notes

Reaction equation

HRID 575448 reaction equation
[I:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:19]3[CH2:20][CH:17]([CH2:18]3)[C:8]3[NH:9][C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:11][C:7]=3[C:6]=2[CH:21]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].Cl[CH2:31][C:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[N:34]([CH3:41])[N:33]=1>CN(C)C=O>[I:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:19]3[CH2:18][CH:17]([CH2:20]3)[C:8]3[N:9]([CH2:31][C:32]4[C:40]5[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=5)[N:34]([CH3:41])[N:33]=4)[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:11][C:7]=3[C:6]=2[CH:21]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 75374703-(chloromethyl)-1-methyl-1H-indazoleHCID 86693505HCID 86693505, compound

Product 1

HCID 86693510HCID 86693510, compoundYield 97.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of ethyl 9-iodo-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate (150 mg, 0.38 mmol), potassium carbonate (79 mg, 0.57 mmol) and sodium iodide (114 mg, 0.76 mmol) was introduced a solution of 3-(chloromethyl)-1-methyl-1H-indazole (137 mg, 0.76 mmol) in N,N-dimethylformamide (5 mL). After warming to 50° C. for 2 hr the reaction mixture was evaporated in vacuo. The residue was suspended in ethyl acetate (40 mL), washed with saturated aqueous sodium bicarbonate (15 mL). After washing the basic aqueous extract with ethyl acetate (3×10 ml), all the organic extracts were combined, washed with water (15 mL) and brine (15 mL), and dried over sodium sulfate. Following filtration of the ethyl acetate extract, the filtrate was evaporated onto silica gel in vacuo. The dry-loaded material was purified by silica gel flash column chromatography (eluent: heptanes/ethyl acetate gradient) to furnish the title compound (198 mg, 0.37 mmol, 97%) as a colorless solid: 1H NMR (500 MHz, CDCl3) δ1.48 (t, J=7.2 Hz, 3H), 1.55-1.57 (m, 2H), 2.79 (dq, J=8.2, 2.8 Hz, 2H), 3.53 (td, J=7.9, 3.8 Hz, 1H), 3.73 (td, J=7.6, 4.1 Hz, 1H), 3.99 (s, 3H), 4.50 (q, J=7.2 Hz, 2H), 6.13 (s, 2H), 6.77 (d, J=7.8 Hz, 1H), 7.05 (ddd, J=7.9, 6.3, 1.3 Hz, 1H), 7.32-7.34 (m, 3H), 7.41 (dd, J=7.9, 1.9 Hz, 1H), 8.89 (s, 1H); M+H=539.

Workup

  1. customwas evaporated in vacuo
  2. washwashed with saturated aqueous sodium bicarbonate (15 mL)
  3. washAfter washing the basic
  4. extractionaqueous extract with ethyl acetate (3×10 ml), all the organic extracts
  5. washwashed with water (15 mL) and brine (15 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltration of the ethyl acetate
  8. extractionextract
  9. customthe filtrate was evaporated onto silica gel in vacuo
  10. customThe dry-loaded material was purified by silica gel flash column chromatography (eluent: heptanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-56c44b7742bd49b88dfcda25551f1bde
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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