Methyl iodide → HCID 58879140, compound

HRID 1365737Notes

Reaction equation

HRID 1365737 reaction equation
[CH2:1]([O:8][C:9]1[C:19](=[O:20])[N:18]2[C:12]([CH2:13][S:14][CH2:15][CH2:16][CH2:17]2)=[N:11][C:10]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.IC.[Li+].[CH3:29][Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH2:1]([O:8][C:9]1[C:19](=[O:20])[N:18]2[C:12]([CH:13]([CH3:29])[S:14][CH2:15][CH2:16][CH2:17]2)=[N:11][C:10]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 58879150HCID 58879150, compound

Product 1

HCID 58879140HCID 58879140, compoundYield 11.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 3-(benzyloxy)-4-oxo-6,7,8,10-tetrahydro-4H-pyrimido[2,1-c][1,4]thiazepine-2-carboxylate (0.180 g, 0.5 mmol) and iodomethane (0.62 mL, 10 mmol) in THF (5 mL) at −78 C was added 1M solution of LiHMDS (1 mL, 1 mmol) over 2 minutes. After 1.5 h, the reaction mixture was quenched with saturated aq. NH4Cl, diluted with EtOAc (50 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by Prep-HPLC to afford the desired product as orange solid (0.021 g, 11%). 1H NMR (500 MHz, CDCl3) δ: 7.48-7.46 (2H, m), 7.37-7.29 (3H, m), 5.24 (2H, s), 5.15 (1H, dd, J=13.9, 4.4 Hz), 4.33 (2H, q, J=7.0 Hz), 4.18 (1H, q, J=7.0 Hz), 3.62 (1H, dd, J=13.6, 12.1 Hz), 3.14-3.09 (1H, m), 2.77 (1H, dt, J=14.4, 4.2 Hz), 2.34-2.27 (1H, m), 1.91-1.82 (1H, m), 1.62 (3H, d, J=7.0 Hz), 1.30 (3H, t, J=7.0 Hz). HRMS (M+H) calcd for C19H23N2O4S: 375.1379; found: 375.1375.

Workup

  1. customthe reaction mixture was quenched with saturated aq. NH4Cl
  2. additiondiluted with EtOAc (50 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-a6600512f0a64c8aadd476d4be317751
Source dataset
uspto-grants-2011_02
Patent number
US07893055B2

Reaction notes

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