Methyl iodide → Tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-yl(methyl)carbamate

HRID 2280936Notes

Reaction equation

HRID 2280936 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH3:36])[C:15](=[O:35])[CH:16]([O:18][C:19]2[N:24]=[C:23]([CH3:25])[C:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[C:21]([CH3:34])[N:20]=2)[CH3:17])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:37][Si]([N-][Si](C)(C)C)(C)C.[K+].CI.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([CH3:36])[C:15](=[O:35])[CH:16]([O:18][C:19]2[N:24]=[C:23]([CH3:25])[C:22]([N:26]([CH3:37])[C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[C:21]([CH3:34])[N:20]=2)[CH3:17])[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 59336090Tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-ylcarbamate

Product 1

HCID 68412900Tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-yl(methyl)carbamateYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a tetrahydrofuran (1 mL) solution of Compound 56 (72 mg), potassium bis(trimethylsilyl)amide (0.5M toluene solution: 273 μL) was added at −78° C. The mixture was stirred at −78° C. for 30 min and methyl iodide (9 μL) was added portionwise. The mixture was then stirred overnight as it was allowed to be slowly warmed to room temperature (20 to 30° C.). Subsequently, a saturated aqueous ammonium chloride solution was added to the reaction mixture and the mixture was extracted twice with chloroform. The organic layer was concentrated under reduced pressure and the resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (ethyl acetate:hexane=1:19 to 1:1) to give 7.7 mg (10% yield) of tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-yl(methyl)carbamate. 2.6 mg (42% yield) of the title compound was synthesized from tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)-amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-yl(methyl)-carbamate in the same manner as in Example 71.

Workup

  1. stirringThe mixture was then stirred overnight as it
  2. temperatureto be slowly warmed to room temperature (20 to 30° C.)
  3. extractionthe mixture was extracted twice with chloroform
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customthe resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (ethyl acetate:hexane=1:19 to 1:1)

Sources & evidence

ORD record
ord-6fc8905ce96845ffa44d750e65819898
Source dataset
uspto-grants-2015_09
Patent number
US09139559B2

Reaction notes

Loading…