Sodium methanethiolate → 3-[2(R)-tert-butoxvcarbonylamino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

HRID 28516Notes

Reaction equation

HRID 28516 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:10][N:11]1[C:16](=[O:17])[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=2[F:26])=[C:14]([CH3:27])[N:13]([CH2:28][C:29]2[C:34](F)=[CH:33][CH:32]=[CH:31][C:30]=2[F:36])[C:12]1=[O:37])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:44][S-:45].[Na+]>CS(C)=O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:10][N:11]1[C:16](=[O:17])[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=2[F:26])=[C:14]([CH3:27])[N:13]([CH2:28][C:29]2[C:34]([S:45][CH3:44])=[CH:33][CH:32]=[CH:31][C:30]=2[F:36])[C:12]1=[O:37])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 4378561Sodium methanethiolate2×HCID 21018394HCID 21018394, compound

Product 1

HCID 210183953-[2(R)-tert-butoxvcarbonylamino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dioneYield 78.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of compound 10a (33 g, 56 mmol) in dry DMSO (100 mL) was added sodium thiomethoxide (4.0 g, 56 mmol) under nitrogen. The reaction mixture was heated to 1000 C under nitrogen for 1 hour. Another 0.28 eq. of sodium thiomethoxide (1.1 g, 16 mmol) was added, and the reaction mixture was heated to 1000 C under nitrogen for 1 hour. The reaction mixture was cooled and partitioned between ethyl ether and water. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine, dried with sodium sulfate, filtered and concentrated. The crude product was purified with a flash chromatography on silica gel eluted with 50% ethyl acetate in hexane to yield compound 10b as a pale yellow solid (27 g, 44 mmol, 78%). HPLC-MS (CI) m/z=524.1 (M+H+-Boc), tR=3.134 (method 4). 1H NMR (CDCl3): 1.38 (s, 9H), 2.07 (s, 3H), 2.51 (s, 3H), 3.90 (s, 3H), 4.07-4.13 (m, 1H), 4.29-4.39 (m, 1H), 5.30-5.53 (m, 2H), 5.79-5.85 (m, 1H), 6.80-6.91 (m, 2H), 6.70 (dd, 1H), 7.06-7.15 (m, 2H), 7.22-7.41 (m, 6h ).

Workup

  1. temperatureThe reaction mixture was heated to 1000 C under nitrogen for 1 hour
  2. temperaturethe reaction mixture was heated to 1000 C under nitrogen for 1 hour
  3. temperatureThe reaction mixture was cooled
  4. custompartitioned between ethyl ether and water
  5. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified with a flash chromatography on silica gel
  10. washeluted with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-8df22d24118c4a5ea314f7538145a41d
Source dataset
uspto-grants-2008_09
Patent number
US07419983B2

Reaction notes

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