Water → HCID 68060043, compound

HRID 1188709Notes

Reaction equation

HRID 1188709 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:13]=1[CH:12]([NH:14][C:15]1[C:20]([CH:21]=O)=[CH:19][N:18]=[C:17]([S:23][CH3:24])[N:16]=1)[CH2:11][CH2:10]2.[OH2:25].[O:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>C(OCC)(=O)C.[Cl-].[Na+].O>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:13]=1[CH:12]([NH:14][C:15]1[C:20](/[CH:21]=[CH:28]/[C:27]([O:26][CH2:30][CH3:29])=[O:25])=[CH:19][N:18]=[C:17]([S:23][CH3:24])[N:16]=1)[CH2:11][CH2:10]2

Participants

7

Reactant 4

HCID 962WaterHCID 8028Tetrahydrofuran3×HCID 24758Sodium hydrideHCID 86662393HCID 86662393, compound

Product 1

HCID 68060043HCID 68060043, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of sodium hydride (60% dispersion, 0.21 g, 5.25 mmol) in anhydrous tetrahydrofuran (21 mL) was added dropwise a solution of triethyl phosphonoacetate (1.03 mL, 1.16 g, 5.19 mmol) in anhydrous tetrahydrofuran (5 mL) at 0-5° C. and the reaction mixture was stirred for 30 min at this temperature. To this suspension was added carefully 4-(7-methoxy-2,3-dihydro-1H-inden-1-ylamino)-2-(methylthio)pyrimidine-5-carbaldehyde (1.48 g, 4.69 mmol) in anhydrous tetrahydrofuran (25 mL) below 5° C. The reaction mixture was allowed to warm to room temperature and stirred for 18 h. The mixture was cooled to below 5° C. and water (22 mL) was added dropwise. It was diluted further with ethyl acetate (25 mL) and saturated brine solution (15 mL), the two phases were separated, and the organic layer was washed with saturated sodium carbonate solution (1×30 mL), water (1×30 mL), dried over sodium sulfate, filtered and evaporated to give (E)-ethyl 3-(4-(7-methoxy-2,3-dihydro-1H-inden-1-ylamino)-2-(methylthio)pyrimidin-5-yl)acrylate as a light brown solid (2.26 g, 5.86 mmol, quant.). ESMS m/z 386 (M+H)+; 1H NMR (400 MHz, CDCl3), E/Z isomers in a ratio of 90:10, δ ppm 8.15 (s, 0.9H, E), 8.13 (s, 0.1H, Z), 7.46 (d, J=16. e.g., 1 Hz, 0.9H, E), 7.27-7.31 (m, 1H, E+Z), 6.92 (d, J=7.5 Hz, 1H, E+Z), 6.76 (d, J=8.3 Hz, 0.9H, E), 6.73 (d, J=8.3 Hz, 0.1H, Z), 6.57 (d, J=11.8 Hz, 0.1H, Z) 6.27 (d, J=16. e.g., 1 Hz, 0.9H, E), 5.98 (d, J=11.8 Hz, 0.1H, Z) 5.77 (d, J=4.5 Hz, 0.9H, E), 5.58-5.65 (m, 1H, E+Z), 5.17 (d, J=4.5 Hz, 0.1H, Z) 4.23 (q, J=7.2 Hz, 2H, E+Z), 3.83 (s, 2.7H, E), 3.78 (s, 0.3H, Z), 2.99-3.11 (m, 1H, E+Z), 2.85-2.95 (m, 1H, E+Z), 2.71-2.82 (m, 1H, E+Z), 2.57 (s, 2.9H, E), 2.56 (s, 0.3H, Z) 1.99-2.11 (m, 1H, E+Z), 1.30 (t, J=7.2 Hz, 3H, E+Z).

Workup

  1. stirringstirred for 18 h
  2. temperatureThe mixture was cooled to below 5° C.
  3. customthe two phases were separated
  4. washthe organic layer was washed with saturated sodium carbonate solution (1×30 mL), water (1×30 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-e6b0412410d54931ab9f982b5626f7d6
Source dataset
uspto-grants-2014_03
Patent number
US08674095B2

Reaction notes

Loading…