Sodium ethoxide → HCID 11676135, compound

HRID 1925210Notes

Reaction equation

HRID 1925210 reaction equation
CN(C)[CH:3]=[CH:4][C:5]([C:7]1[N:14]2[C:10]([O:11][CH:12]=[CH:13]2)=[N:9][C:8]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])=O.Cl.[N:24]12[CH2:31][CH2:30][CH:27]([CH2:28][CH2:29]1)[C@@H:26]([NH:32][C:33]([NH2:35])=[NH:34])[CH2:25]2.[O-]CC.[Na+]>C(O)C>[Cl:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:8]1[N:9]=[C:10]2[N:14]([C:7]=1[C:5]1[CH:4]=[CH:3][N:35]=[C:33]([NH:32][C@@H:26]3[CH:27]4[CH2:28][CH2:29][N:24]([CH2:31][CH2:30]4)[CH2:25]3)[N:34]=1)[CH:13]=[CH:12][O:11]2

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 67519860HCID 67519860, compoundHCID 178479479HCID 178479479, compound

Product 1

HCID 11676135HCID 11676135, compoundYield 78.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 3-(dimethylamino)-1-[6-(2-chlorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-one (316 mg, 1.0 mmol) and (R)—N-1-azabicyclo[2.2.2]oct-3-ylguanidine hydrochloride (427 mg, 2.0 mmol) is diluted with 5 ml of absolute ethanol and treated with 1.8 eq. of a 21% w/w solution of sodium ethoxide in ethanol (0.6 ml) to form a reaction mixture. The reaction mixture is heated to reflux for 24 hours. Volatiles are removed in vacuo and the residue is taken up in 12 ml of a 5:1 mixture of ethyl acetate and methanol, washed twice with 5 ml each of water, and then with a saturated sodium chloride solution (5 ml). The organic phase is dried with magnesium sulfate, filtered and concentrated in vacuo, to give a brown oil. The product is purified by flash chromatography on silica gel (ethyl acetate/methanol/ammonium hydroxide solution, 20:4:1) to yield 329 mg of a pale yellow solid (78%). M.p.=132-134° C.; 300 MHz 1H NMR (DMSO-d6) δ: 8.91 (s, 1H), 8.25 (s, 1H), 8.03 (d, J=5.1 Hz, 1H), 7.63-7.45 (m, 4H), 7.38 (d, J=6.9 Hz, 1H), 5.80 (br. s, 1H), 3.87 (m, 1H), 3.16 (br. s, 1H), 2.86 (m, 1H), 2.8-2.4 (m, 4H), 1.92 (br. s, 1H), 1.83 (br. s, 1H), 1.59 (m, 2H), 1.32 (br. s, 1H). LCMS: 421 [M+H]; calc. for C22H21ClN6O 0.1 EtOAc 0.75 H2O: C, 60.70; H, 5.30; N, 18.98; found. C, 61.17; H, 5.21; N, 18.68.

Workup

  1. customto form a reaction mixture
  2. temperatureThe reaction mixture is heated
  3. temperatureto reflux for 24 hours
  4. customVolatiles are removed in vacuo
  5. additionthe residue is taken up in 12 ml of a 5:1 mixture of ethyl acetate and methanol
  6. washwashed twice with 5 ml each of water
  7. dry with materialThe organic phase is dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a brown oil
  11. customThe product is purified by flash chromatography on silica gel (ethyl acetate/methanol/ammonium hydroxide solution, 20:4:1)

Sources & evidence

ORD record
ord-f31a37be8c5a48bcbf115aaa8e447ff9
Source dataset
uspto-grants-2012_05
Patent number
US08178672B2

Reaction notes

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