Methyl iodide → HCID 66673526, compound

HRID 423560Notes

Reaction equation

HRID 423560 reaction equation
IC.[F:3][C:4]([F:9])([F:8])[C:5]([OH:7])=[O:6].[CH3:10][CH:11]([C:13]1[N:17]=[C:16]([N:18]2[CH2:23][CH2:22][CH:21]([CH2:24][O:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]4[CH:37]=[CH:36][C:35]([S:38]([NH:41][CH2:42][CH2:43][N:44]5[CH2:49][CH2:48][O:47][CH2:46][CH2:45]5)(=[O:40])=[O:39])=[CH:34][CH:33]=4)=[CH:28][CH:27]=3)[CH2:20][CH2:19]2)[O:15][N:14]=1)[CH3:12].[OH-].[K+]>CCO>[C:5]([OH:7])([C:4]([F:9])([F:8])[F:3])=[O:6].[F:3][C:4]([F:9])([F:8])[C:5]([OH:7])=[O:6].[CH3:4][N:41]([CH2:42][CH2:43][N:44]1[CH2:45][CH2:46][O:47][CH2:48][CH2:49]1)[S:38]([C:35]1[CH:36]=[CH:37][C:32]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH2:24][CH:21]3[CH2:20][CH2:19][N:18]([C:16]4[O:15][N:14]=[C:13]([CH:11]([CH3:10])[CH3:12])[N:17]=4)[CH2:23][CH2:22]3)=[CH:27][CH:28]=2)=[CH:33][CH:34]=1)(=[O:40])=[O:39]

Participants

6

Reactant 3

HCID 6328Methyl iodide3×HCID 14797Potassium HydroxideHCID 66672589HCID 66672589, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.05%HCID 66673526HCID 66673526, compoundYield 116.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Iodomethane (0.004 mL, 0.07 mmol) was added to a solution of 4′-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-N-[2-(4-morpholinyl)ethyl]-4-biphenylsulfonamide trifluoroacetate (Example 109, 46 mg, 0.07 mmol) and KOH (12 mg, 0.21 mmol) in EtOH (1 mL) at ambient temperature. The mixture was stirred at ambient temperature overnight. The mixture was charged with additional iodomethane (0.006 mL, 0.11 mmol), and stirred at ambient temperature overnight. The mixture was charged with additional iodomethane (0.006 mL, 0.11 mmol) and stirred at ambient temperature overnight. The mixture was quenched with MeOH and concentrated. The crude product was purified by reverse-phase preparative HPLC using a CH3CN:H2O gradient (0.5:99.5 to 90:10) with 0.05% TFA as a modifier to give 19 mg (39%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.80-7.75 (m, 2H), 7.71-7.66 (m, 2H), 7.52 (d, 2H, J=8.8 Hz), 6.97 (d, 2H, J=8.8 Hz), 4.25-4.15 (m, 2H), 4.07-3.83 (m, 6H), 3.78-3.55 (m, 3H), 3.51-3.32 (m, 4H), 3.17-2.97 (m, 3H), 2.95-2.85 (m, 1H), 2.80 (s, 3H), 2.14-2.02 (m, 1H), 2.01-1.91 (m, 2H), 1.54-1.39 (m, 2H), 1.27 (d, 6H, J=7.0 Hz); LRMS (ESI), m/z 584 (M+H).

Workup

  1. stirringstirred at ambient temperature overnight
  2. stirringstirred at ambient temperature overnight
  3. customThe mixture was quenched with MeOH
  4. concentrationconcentrated
  5. customThe crude product was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-2cb6311d0700429aa4ea9c2f8736920e
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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