Ethyl Acetate → tert-butyl (3-(5-methyl-2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

HRID 527399Notes

Reaction equation

HRID 527399 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][CH2:12][O:13]C(C)=O.[C:17]([C:20]1[C:21]([NH:28][C:29]2[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:32]=[CH:33][CH:34]=2)=[N:22][C:23]([S:26][CH3:27])=[N:24][CH:25]=1)(=O)[CH3:18]>C1COCC1>[CH3:18][C:17]1[C:20]2[CH:25]=[N:24][C:23]([S:26][CH3:27])=[N:22][C:21]=2[N:28]([C:29]2[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:32]=[CH:33][CH:34]=2)[C:12](=[O:13])[CH:11]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2733832Lithium HexamethyldisilazideHCID 86732010Tert-butyl (3-((5-acetyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate

Product 1

HCID 86732009tert-butyl (3-(5-methyl-2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamateYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiHMDS (1.0 M in THF, 27.3 mL, 27.3 mmol) was added to THF (100 mL) at −78° C. and treated with EtOAc (2.50 mL, 25.6 mmol) and stirred 15 min. tert-Butyl (3-((5-acetyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (53) (3.19 g, 8.52 mmol) was added in one portion at −78° C. and the solution warmed to RT and stirred for 3 h. The reaction mixture was quenched with a saturated solution of NH4Cl and extracted with EtOAc (150 mL), washed with brine and dried over MgSO4, filtered and concentrated. Purification of the crude residue on silica gel column (10-90% EtOAc in hexanes) afforded the title compound (54) (2.49 g, 6.25 mmol, 73% yield) as a light yellow amorphous solid. m/z (ESI, +ve ion) 398.9 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 8.72 (1H, s), 7.46 (1H, br. s.), 7.42 (1H, t, J=8.0 Hz), 7.31 (1H, dd, J=8.2, 1.4 Hz), 6.87-6.94 (1H, m), 6.50-6.59 (2H, m), 2.50 (3H, d, J=1.0 Hz), 2.17 (3H, s), 1.50 (9H, s).

Workup

  1. additionwas added in one portion at −78° C.
  2. customThe reaction mixture was quenched with a saturated solution of NH4Cl
  3. extractionextracted with EtOAc (150 mL)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude residue on silica gel column (10-90% EtOAc in hexanes)

Sources & evidence

ORD record
ord-33306a6caa304968a9d7e0f866a6c5ba
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

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