Sodium Iodide → ethyl 8-fluoro-9-iodo-3((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate

HRID 575438Notes

Reaction equation

HRID 575438 reaction equation
[F:1][C:2]1[C:21]([I:22])=[CH:20][C:5]2[C:6]3[N:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8][C:7]=3[CH:16]3[CH2:19][CH:18]([C:4]=2[CH:3]=1)[CH2:17]3.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].Cl[CH2:32][C:33]1[N:37]([CH3:38])[N:36]=[CH:35][CH:34]=1>CN(C)C=O>[F:1][C:2]1[C:21]([I:22])=[CH:20][C:5]2[C:6]3[N:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]([CH2:32][C:33]4[N:37]([CH3:38])[N:36]=[CH:35][CH:34]=4)[C:7]=3[CH:16]3[CH2:19][CH:18]([C:4]=2[CH:3]=1)[CH2:17]3

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 128450475-(Chloromethyl)-1-methyl-1H-pyrazoleHCID 86693491Ethyl 8-fluoro-9-iodo-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate

Product 1

HCID 86693496ethyl 8-fluoro-9-iodo-3((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of ethyl 8-fluoro-9-iodo-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxylate (100 mg at 69% purity LCMS-UV215), potassium carbonate (50 mg, 0.36 mmol) and sodium iodide (73 mg, 0.48 mmol) was introduced a solution of 5-(chloromethyl)-1-methylpyrazole (64 mg, 0.48 mmol) in N,N-dimethylformamide (5 mL). After warming to 50° C. for 4 hr the reaction mixture was evaporated in vacuo. The residue was suspended in ethyl acetate (40 mL), washed with saturated aqueous sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (10 mL) and the organic extract dried over sodium sulfate. Following filtration, the filtrate was evaporated onto silica gel in vacuo and the dry-loaded material purified by silica gel flash column chromatography (eluent: heptanes/ethyl acetate gradient). The title compound (78 mg, 0.15 mmol, 88%) was furnished as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 1.45 (t, J=7.3 Hz, 3H), 1.67-1.74 (m, 2H), 2.92 (dq, J=8.2, 2.8 Hz, 2H), 3.38 (dt, J=7.3, 3.8 Hz, 1H), 3.58 (dt, J=8.2, 3.8 Hz, 1H), 3.92 (s, 3H), 4.42 (q, J=6.9 Hz, 2H), 5.59 (d, J=1.6 Hz, 1H), 5.74 (s, 2H), 6.82 (d, J=8.9 Hz, 1H), 7.34 (d, J=1.8 Hz, 1H), 8.86 (d, J=6.9 Hz, 1H); M+1=507.

Workup

  1. customwas evaporated in vacuo
  2. washwashed with saturated aqueous sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (10 mL)
  3. extractionthe organic extract
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltration
  6. customthe filtrate was evaporated onto silica gel in vacuo
  7. customthe dry-loaded material purified by silica gel flash column chromatography (eluent: heptanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-68b2f2c5f5374f09972c2b15b817b847
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…