Potassium Hydroxide → HCID 86617872, compound

HRID 2426797Notes

Reaction equation

HRID 2426797 reaction equation
[CH:1]([C:3]1[CH:8]=[C:7]([N:9]([CH3:15])[CH2:10][CH:11]2[CH2:13][CH:12]2[CH3:14])[N:6]=[C:5]([N:16]([CH3:21])[S:17]([CH3:20])(=[O:19])=[O:18])[CH:4]=1)=[O:2].[I-].[CH3:23][S+](C)C.[OH-].[K+]>C(#N)C.O.CCOC(C)=O>[CH3:21][N:16]([C:5]1[CH:4]=[C:3]([CH:1]2[CH2:23][O:2]2)[CH:8]=[C:7]([N:9]([CH3:15])[CH2:10][CH:11]2[CH2:13][CH:12]2[CH3:14])[N:6]=1)[S:17]([CH3:20])(=[O:18])=[O:19]

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 75127Trimethylsulfonium iodideHCID 86617871HCID 86617871, compound

Product 1

HCID 86617872HCID 86617872, compound

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of N-(4-formyl-6-{methyl[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-methylmethanesulfonamide (435 mg, 1.40 mmol) in acetonitrile (5 mL) was added 5 drops water, trimethylsulfonium iodide (342 mg, 1.68 mmol) and potassium hydroxide (188 mg, 3.35 mmol). The reaction was stirred at 65° C., sealed, for 3 h, diluted with EtOAc, washed with sat'd aq NaHCO3, brine, dried over sodium sulfate, and concentrated in vacuo to provide N-methyl-N-(6-{methyl[(2-methylcyclopropyl)methyl]amino}-4-oxiran-2-ylpyridin-2-yl)methanesulfonamide, used as is in the next step. A solution of N-methyl-N-(6-{methyl[(2-methylcyclopropyl)methyl]amino}-4-oxiran-2-ylpyridin-2-yl)methanesulfonamide (440 mg, 1.35 mmol) in EtOH (10 mL) and NH4OH (15 mL) was stirred at 60° C., sealed, for 16 h, concentrated in vacuo and purified by flash chromatography (silica, 5-15% (10% NOH/MeOH)/CH2Cl2) to provide N-(4-(2-amino-1-hydroxyethyl)-6-{methyl[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-methylmethanesulfonamide as a thick oil. 1H NMR (400 MHz, CD3OD) δ 6.52 (s, 1H), 6.47 (s, 1H), 4.58 (X′ of A′B′X′, dd, J=7.6, 4.0 Hz, 2H), 3.54 (A of ABX, dd, J=14.4, 6.4 Hz, 1H), 3.35 (B of ABX, dd, J=14.4, 6.8 Hz, 1H), 3.30 (s, 3H), 3.13 (s, 3H), 3.08 (s, 3H), 3.86 (A′ of A′B′X′, dd, J=13.2, 4.0 Hz, 1H), 2.76 (B′ of A′B′X′, dd, J=13.2, 7.6 Hz, 1H), 1.02 (d, J=6.0 Hz, 3H), 0.80-0.65 (m, 2H), 0.46-0.39 (m, 1H), 0.25-0.18 (m, 1H).

Workup

  1. customsealed, for 3 h
  2. washwashed with sat'd aq NaHCO3, brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b0f46e9cbad54dc7aa1cd8169a3a3f1d
Source dataset
uspto-grants-2011_06
Patent number
US07968571B2

Reaction notes

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