Methyl iodide → HCID 86695207, compound

HRID 1504050Notes

Reaction equation

HRID 1504050 reaction equation
[C:1]([CH2:3][C@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([O:16][CH:17]4[CH2:22][CH2:21][C:20]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:23])[CH2:19][CH2:18]4)[C:6]=3[C:5]1=2)#[N:2].[H-].[Na+].[CH3:34]I>CN(C=O)C>[C:1]([CH2:3][C@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([O:16][CH:17]4[CH2:18][CH2:19][C:20]([N:24]([CH3:34])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:23])[CH2:21][CH2:22]4)[C:6]=3[C:5]1=2)#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86695203HCID 86695203, compound

Product 1

HCID 86695207HCID 86695207, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 50-mL round-bottom flask containing a solution of tert-butyl N-(4-[[(3R)-3-(cyanomethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]-1-methylcyclohexyl)carbamate (100 mg, 0.23 mmol, 1.00 equiv) in distilled DMF (3 mL) was added sodium hydride (60% dispersion in mineral oil 37 mg, 0.93 mmol, 4.09 equiv) at 0° C. The resulting solution was stirred for 0.5 h at this temperature. Then CH3I (321 mg, 2.26 mmol, 1.00 equiv) was added and the resulting solution was allowed to react, with stirring, for an additional 2 h at 30° C. The reaction was then quenched with saturated aqueous NH4Cl and extracted with 3×30 mL of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2) to give tert-butyl N-(4-[[(3R)-3-(cyanomethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]-1-methylcyclohexyl)-N-methylcarbamate (80 mg, 78%) as a white solid.

Workup

  1. customto react
  2. stirringwith stirring, for an additional 2 h at 30° C
  3. customThe reaction was then quenched with saturated aqueous NH4Cl
  4. extractionextracted with 3×30 mL of ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-74676d8da76e4d22907eec552cb11b91
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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