Dimethylformamide → HCID 68985429, compound

HRID 1467878Notes

Reaction equation

HRID 1467878 reaction equation
[NH2:1][CH:2]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][CH:30]=1)[C:3]([N:5]1[CH2:10][CH2:9][CH:8]([N:11]([CH:25]2[CH2:27][CH2:26]2)[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)(=[O:14])=[O:13])[CH2:7][CH2:6]1)=[O:4].CI.[CH3:39]N(C=O)C.[H-].[Na+]>C(OCC)(=O)C>[C:35]([C:32]1[CH:31]=[CH:30][C:29]([CH2:28][CH:2]([NH:1][CH3:39])[C:3]([N:5]2[CH2:6][CH2:7][CH:8]([N:11]([CH:25]3[CH2:26][CH2:27]3)[S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:24])[F:23])[CH:16]=3)(=[O:13])=[O:14])[CH2:9][CH2:10]2)=[O:4])=[CH:34][CH:33]=1)#[N:36]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68986570HCID 68986570, compound

Product 1

HCID 68985429HCID 68985429, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-{1-[2-amino-3-(4-cyanophenyl)propionyl]piperidin-4-yl}-N-cyclopropyl-3-trifluoromethylbenzenesulfonamide (see Example 13, 300 mg, 0.58 mmol), MeI (830 mg, 5.9 mmol), and DMF (5 mL) was treated with NaH (67 mg, 60% mineral oil, 1.8 mmol) at room temperature for 20 hours. The reaction mixture was diluted with ethyl acetate (20 mL), and washed with water (5 mL) and brine (5 mL). The organic layer was evaporated and the residue was purified by column (silica gel, EtOAc/hexane 1/1) to give the title compound N-{1-[3-(4-cyanophenyl)-2-methylamino-propionyl]piperidin-4-yl}-N-cyclopropyl-3-trifluoromethyl-benzenesulfonamide (26) as free base, which was dissolved in 1,4-dioxane (4 mL), and treated with HCl solution (4N in 1,4-dioxane, 1 mL). The resulting mixture was triturated with ethyl ether (10 mL), and the precipitated material was collected by filtration, washed with ethyl ether (2×5 mL), and dried under vacuum for 12 hours to afford the title compound 26 as a HCl-salt (white solid, 0.2 g, yield 65%). 1H NMR (HCl-salt, CD3OD): δ 8.12-8.19 (m, 2H), 8.03 (d, 1H, J=9.2 Hz), 7.86 (dd, 1H, J=7.7 & 7.8 Hz), 7.77 (dd, 2H, J=4.3 & 8.1 Hz), 7.49 (dd, 2H, J=1.9 & 8.3 Hz), 4.76-4.79 (m, 1H), 4.52-4.59 (m, 1H), 3.96-4.06 (m, 1H), 3.6-3.7 (m, 1H), 3.34-3.38 (m, 1H), 3.06-3.14 (m, 2H), 2.68-2.72 (m, 3H, NCH3), 2.34-2.65 (m, 2H), 1.52-2.02 (m, 4H), 0.62-0.92 (m, 4H). LC: 100%. MS (e/z): 535 (m+1).

Workup

  1. washwashed with water (5 mL) and brine (5 mL)
  2. customThe organic layer was evaporated
  3. customthe residue was purified by column (silica gel, EtOAc/hexane 1/1)

Sources & evidence

ORD record
ord-dde48122b4dc4d7a98771e3057a6fb28
Source dataset
uspto-grants-2015_04
Patent number
US09000174B2

Reaction notes

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