Triethylamine → 4-(5-Bromo-2-(methylthio)pyrimidine-6-carboxamido)pyridin-3-yl diethylcarbamodithioate

HRID 2267318Notes

Reaction equation

HRID 2267318 reaction equation
[Br:1][C:2]1[C:3]([C:10]([OH:12])=O)=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[CH2:26]([N:28]([CH2:39][CH3:40])[C:29]([S:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][C:37]=1[NH2:38])=[S:30])[CH3:27]>CN(C)C=O.ClCCl>[CH2:39]([N:28]([CH2:26][CH3:27])[C:29]([S:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][C:37]=1[NH:38][C:10]([C:3]1[N:4]=[C:5]([S:8][CH3:9])[N:6]=[CH:7][C:2]=1[Br:1])=[O:12])=[S:30])[CH3:40]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2917865-Bromo-2-(methylthio)pyrimidine-4-carboxylic AcidHCID 146662264-Aminopyridin-3-yl diethylcarbamodithioate

Product 1

HCID 602043714-(5-Bromo-2-(methylthio)pyrimidine-6-carboxamido)pyridin-3-yl diethylcarbamodithioateYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A catalytic amount of N,N-dimethylformamide (2 drops) was added to a stirred suspension of 5-bromo-2-(methylthio)pyrimidine-4-carboxylic acid (2.07 g, 8.33 mmol) and a 2 M solution of oxalyl chloride (21 mL, 0.042 mol) in dichloromethane under nitrogen at r.t. Vigorous effervescence was observed. After 30 min everything had dissolved and the solvent was then evaporated in vacuo. The residue was dissolved in dichloromethane (20 mL) and placed under nitrogen. Triethylamine (2.32 mL, 16.66 mmol) was added to this stirred solution at r.t. followed by 4-aminopyridin-3-yl diethylcarbamodithioate (2.01 g, 8.33 mmol). Everything quickly dissolved with a noticeable exotherm. After 3 h at r.t. tlc showed a new major product. The reaction was diluted with dichloromethane (20 mL) and washed with a saturated aqueous solution of sodium hydrogen carbonate (40 mL). The organic layer was separated, dried over sodium sulfate, filtered and the solvent evaporated in vacuo. The residue was purified by flash chromatography (ethyl acetate/hexane 15:85 to 60:40) to yield 4-(5-bromo-2-(methylthio)pyrimidine-6-carboxamido)pyridin-3-yl diethylcarbamodithioate (1.99 g, 51%) as a pale yellow amorphous solid. 1H NMR: δ (CDCl3, 400 MHz) 1.30 (t, J=7 Hz, 3 H), 1.51 (t, J=7 Hz, 3 H), 2.60 (s, 3 H), 3.93-4.08 (m, 4 H), 8.57-8.62 (m, 2 H), 8.69 (d, J=6 Hz, 1 H), 8.85 (s, 1 H), 10.67 (s, 1 H).

Workup

  1. customat r.t
  2. dissolutionAfter 30 min everything had dissolved
  3. customthe solvent was then evaporated in vacuo
  4. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  5. dissolutionEverything quickly dissolved with a noticeable exotherm
  6. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (40 mL)
  7. customThe organic layer was separated
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent evaporated in vacuo
  11. customThe residue was purified by flash chromatography (ethyl acetate/hexane 15:85 to 60:40)

Sources & evidence

ORD record
ord-b2fed5bea7b34f8ca13013b5750f4bf9
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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