Methyl iodide → HCID 59149748, compound

HRID 1675138Notes

Reaction equation

HRID 1675138 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][NH:9][C:10](=[O:36])[C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:24]=[CH:25][C:26]4[N:27]([C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][N:31]=4)[N:28]=3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1.[H-].[Na+].I[CH3:40]>CN(C=O)C>[CH3:40][N:9]([CH2:8][CH2:7][N:3]1[CH2:4][CH2:5][CH2:6][C:2]1=[O:1])[C:10](=[O:36])[C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:18][CH2:19][N:20]([C:23]3[CH:24]=[CH:25][C:26]4[N:27]([C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][N:31]=4)[N:28]=3)[CH2:21][CH2:22]2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 44125880HCID 44125880, compound

Product 1

HCID 59149748HCID 59149748, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of N-[2-(2-oxopyrrolidin-1-yl)ethyl]-4-[1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]benzamide (obtained as described in Example 639) (150 mg, 0.30 mmol) in DMF (2 mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil) (13.16 mg, 0.33 mmol) in DMF (1 mL) under nitrogen. The resulting suspension was stirred at ambient temperature for 5 minutes, then iodomethane (0.028 mL, 0.45 mmol) was added and the mixture was stirred at ambient temperature for a further 10 minutes. The reaction was quenched with MeOH (0.5 mL) and purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-methyl-N-[2-(2-oxopyrrolidin-1-yl)ethyl]-4-[1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]benzamide (84 mg, 55%) as a solid.

Workup

  1. stirringthe mixture was stirred at ambient temperature for a further 10 minutes
  2. customThe reaction was quenched with MeOH (0.5 mL)
  3. custompurified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  4. additionFractions containing the desired compound
  5. customwere evaporated to dryness

Sources & evidence

ORD record
ord-d702edffba184cc5b5d2981d8f5b400f
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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