Sodium ethoxide → Tert-butyl 4-({4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}amino)piperidine-1-carboxylate

HRID 1783811Notes

Reaction equation

HRID 1783811 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][C:18]([F:21])=[CH:17][CH:16]=1)=O.Cl.[NH2:24][C:25]([NH:27][CH:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1)=[NH:26].[O-]CC.[Na+]>C(O)C>[F:21][C:18]1[CH:17]=[CH:16][C:15]([C:8]2[N:9]=[C:10]3[N:14]([C:7]=2[C:5]2[CH:4]=[CH:3][N:24]=[C:25]([NH:27][CH:28]4[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]4)[N:26]=2)[CH:13]=[CH:12][O:11]3)=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 675198943-(Dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-oneHCID 178452101HCID 178452101, compound

Product 1

HCID 57590685Tert-butyl 4-({4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}amino)piperidine-1-carboxylateYield 65.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 3-(dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-one (4.24 g, 14.2 mmol) and tert-butyl 4-{[amino(imino)methyl]amino}-piperidine-1-carboxylate hydrochloride (5.92 g, 21.2 mmol) was diluted with 40 ml of absolute ethanol and treated with 1.35 eq. of a 21% w/w solution of sodium ethoxide in ethanol (7.2 ml) to form a reaction mixture. The reaction mixture was heated to reflux for 15 hours. Volatiles were removed in vacuo and the residue was taken up in 200 ml of ethyl acetate, washed twice with 100 ml each of water, and then with a saturated sodium chloride solution (100 ml). The organic phase was dried with magnesium sulfate, filtered and concentrated in vacuo, to give a brown solid. The product was purified by flash chromatography on silica gel (gradient 50%-75% ethyl acetate/hexanes) to yield 4.436 g of a tan solid (65%). M.p.=175° C.; 300 MHz 1H NMR (CDCl3) δ: 8.06 (s, 1H), 8.04 (s, 1H), 7.65-7.60 (m, 2H), 7.48 (d, J=1.6 Hz, 1H), 7.17-7.13 (m, 2H), 6.52 (d, J=5.6 Hz, 1H), 5.1 (br. s, 1H), 4.2-3.9 (m, 3H), 2.2-2.0 9M, 2H), 16.-1.4 (m, 4H), 1.48 (s, 9H). LCMS: 479 [M+H]; calc. for C25H27FN6O3.0.25H2O: C, 62.11; H, 5.74; N, 17.39. Found C, 62.43; H, 5.37; N, 17.35.

Workup

  1. customto form a reaction mixture
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 15 hours
  4. customVolatiles were removed in vacuo
  5. washwashed twice with 100 ml each of water
  6. dry with materialThe organic phase was dried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown solid
  10. customThe product was purified by flash chromatography on silica gel (gradient 50%-75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8ff1923098a748439b8056f3c337bda7
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

Loading…