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 1827937Notes

Reaction equation

HRID 1827937 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

Conditions

Temperature
100 °C

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 100° 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 100° 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 100° C. under nitrogen for 1 hour
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between ethyl ether and water
  4. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified with a flash chromatography on silica gel
  9. washeluted with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-13e2081c6ece4e2c946961e89d2df734
Source dataset
uspto-grants-2006_06
Patent number
US07056927B2

Reaction notes

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