Methyl iodide → HCID 69060147, compound

HRID 1435923Notes

Reaction equation

HRID 1435923 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C@@H:13]2[CH2:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][C@@H:12]2[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([C:24]([F:27])([F:26])[F:25])[C:6]=2[NH:5]1.Cl.F[C:30](F)(F)C1C2NC(=O)[C@@H]3CNC[C@@H]3C=2C=CC=1.IC>C1COCC1>[CH3:30][N:5]1[C:6]2[C:7]([C:24]([F:27])([F:25])[F:26])=[CH:8][CH:9]=[CH:10][C:11]=2[CH:12]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:14][CH:13]2[C:4]1=[O:3]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69060208HCID 69060208, compoundHCID 69062613HCID 69062613, compound

Product 1

HCID 69060147HCID 69060147, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (40 mg of 60% dispersion in mineral oil, 1.0 mmol) in 5 mL of THF was added (±)-cis-tert-butyl 4-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]quinoline-2(9bH)-carboxylate, the intermediate from Example 3 (80 mg, 0.22 mmol) in 3 mL of THF. The mixture was stirred for 30 min and then there was added iodomethane (0.10 mL, 1.6 mmol) and the resulting mixture was allowed to stir at ambient temperature for 18 h. The reaction was filtered through a pad of silica gel and concentrated. The residue was purified by chromatography (ISCO, elution with 1-10% EtOAc in hexane) to afford tert-butyl 5-methyl-4-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]quinoline-2(9bH)-carboxylate. To this material in 4 mL of hexane was added HCl (4 mL of a 4N solution in 1,4-dioxane, 16 mmol) and the resulting solution was allowed to stir at ambient temperature overnight. The solvents were removed in vacuo and the residue was purified by HPLC (C18 reverse phase, elution with gradient H2O/CH3CN+0.5% TFA). Pure fractions were combined and concentrated. The residue was partitioned between aq NH4OH and CHCl3, the organics were washed with brine, dried (K2CO3) and concentrated to afford 12 mg (60%) of the title compound of Example 4. 1H NMR (CDCl3): δ 7.60 (d, 1H), 7.42 (d, 1H), 7.18 (t, 1H), 3.81 (dd, 1H), 3.39 (s, 3H), 3.37-30 (m, 2H), 3.22-3.18 (m, 1H), 3.05-2.98 (m, 1H), 2.81 (t, 1H). LRMS (ESI): 271.16 (M+H)+.

Workup

  1. stirringto stir at ambient temperature for 18 h
  2. filtrationThe reaction was filtered through a pad of silica gel
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography (ISCO, elution with 1-10% EtOAc in hexane)

Sources & evidence

ORD record
ord-7496bc48827a4a84a452e0ad1b6b4748
Source dataset
uspto-grants-2009_11
Patent number
US07618980B2

Reaction notes

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