Methyl iodide → HCID 67431982, compound

HRID 410605Notes

Reaction equation

HRID 410605 reaction equation
[C:1]([O:5][C:6]([N:8]([C:28]1[N:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=1)[C:9]1[CH:10]=[C:11]([C:16]2[S:20][C:19]([CH2:21][C@@H:22]([CH3:27])[C:23]([O:25][CH3:26])=[O:24])=[N:18][CH:17]=2)[CH:12]=[C:13]([CH3:15])[CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CI.[Li+].[CH3:41][Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[C:1]([O:5][C:6]([N:8]([C:28]1[N:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[CH:30][N:29]=1)[C:9]1[CH:10]=[C:11]([C:16]2[S:20][C:19]([CH2:21][C:22]([CH3:41])([CH3:27])[C:23]([O:25][CH3:26])=[O:24])=[N:18][CH:17]=2)[CH:12]=[C:13]([CH3:15])[CH:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 67431495HCID 67431495, compound

Product 1

HCID 67431982HCID 67431982, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The product from Step 1 (700 mg, 1.305 mmol) and methyl iodide (926 mg, 6.52 mmol) were taken up in THF (18 mL) at room temperature, and LHMDS (1.0 M in THF, 6.52 mL, 6.52 mmol) was added dropwise. After stirring for 1 h at room temperature, the reaction was quenched with saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. Flash chromatography (0-50% ethyl acetate in hexanes) afforded methyl 3-[5-(3-{(tert-butoxycarbonyl)[4-(trifluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethylpropanoate (324 mg, 45%) as a yellow gum. MS ESI: [M+H]+ m/z 551.1.

Workup

  1. customthe reaction was quenched with saturated NH4Cl
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-af37a000d8324300b144eaf415c91af9
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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