Sodium ethoxide → HCID 57463068, compound

HRID 1783803Notes

Reaction equation

HRID 1783803 reaction equation
CN(C)[CH:3]=[CH:4][C:5]([C:7]1[N:14]2[C:10]([S:11][CH:12]=[CH:13]2)=[N:9][C:8]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1)=O.Cl.[NH2:25]/[C:26](/[NH:29][C@@H:30]1[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]1)=[N:27]/[H].[O-]CC.[Na+]>C(O)C>[CH3:22][O:21][C:17]1[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:27]=[C:26]([NH:29][C@@H:30]4[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]4)[N:25]=2)[CH:13]=[CH:12][S:11]3)[CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 67519890HCID 67519890, compoundHCID 178478974HCID 178478974, compound

Product 1

HCID 57463068HCID 57463068, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 3-(dimethylamino)-1-[6-(3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]prop-2-en-1-one (5.0 g, 15.3 mmol) and tert-butyl (3R)-3-{[(Z)-amino(imino)methyl]amino}piperidine-1-carboxylate hydrochloride (5.28 g, 18.95 mmol) was diluted with 60 ml of absolute ethanol and treated with 1.15 eq. of a 21% w/w solution of sodium ethoxide in ethanol (6.56 ml) to form a reaction mixture. The reaction mixture was heated to reflux for 24 hours. Volatiles were removed in vacuo and the residue was taken up in 250 ml of ethyl acetate and 250 ml of water. The phases were separated and the aqueous phase was extracted with 250 ml of ethyl acetate. The combined organic extracts were washed with 250 ml each of water, and then with a saturated sodium chloride solution (250 ml). The organic phase was dried with magnesium sulfate, filtered and concentrated in vacuo, to give a yellow oil. The product was purified by flash chromatography on silica gel (ethyl acetate/hexanes, 50%) to yield 7.2 g of a pale yellow solid (93%). 300 MHz 1H NMR (DMSO-d6 at 80° C.) δ: 8.69 (d, J=3.5 Hz, 1H), 8.10 (d, J=5.3 Hz, 1H), 7.32-7.41 (m, 2H), 7.12-7.18 (m, 2H), 6.91-7.02 (m, 2H), 6.41 (d, J=5.3 Hz, 1H), 3.94 (br. d, J=7.0, 1H), 3.74-3.88 (m, 1H), 3.78 (s, 3H), 3.67 (br. d, J=13.2, 1H), 2.86-3.02 (m, 2H), 1.90-2.06 (m, 1H), 1.70-1.84 (m, 1H), 1.38-1.64 (m, 2H), 1.34 (s, 9H). LCMS: 507 [M+H].

Workup

  1. customto form a reaction mixture
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 24 hours
  4. customVolatiles were removed in vacuo
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with 250 ml of ethyl acetate
  7. washThe combined organic extracts were washed with 250 ml each of water
  8. dry with materialThe organic phase was dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a yellow oil
  12. customThe product was purified by flash chromatography on silica gel (ethyl acetate/hexanes, 50%)

Sources & evidence

ORD record
ord-f1a8089dfcd943e1bc3475841cbcbb9f
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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