Sodium ethoxide → HCID 57463068, compound

HRID 1925217Notes

Reaction equation

HRID 1925217 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) is 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 is heated to reflux for 24 hours. Volatiles are removed in vacuo and the residue is taken up in 250 ml of ethyl acetate and 250 ml of water. The phases are separated and the aqueous phase is extracted with 250 ml of ethyl acetate. The combined organic extracts are washed with 250 ml each of water, and then with a saturated sodium chloride solution (250 ml). The organic phase is dried with magnesium sulfate, filtered and concentrated in vacuo, to give a yellow oil. The product is 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 is heated
  3. temperatureto reflux for 24 hours
  4. customVolatiles are removed in vacuo
  5. customThe phases are separated
  6. extractionthe aqueous phase is extracted with 250 ml of ethyl acetate
  7. washThe combined organic extracts are washed with 250 ml each of water
  8. dry with materialThe organic phase is dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a yellow oil
  12. customThe product is purified by flash chromatography on silica gel (ethyl acetate/hexanes, 50%)

Sources & evidence

ORD record
ord-bb10b3049c3b4fb2a586e730da664ea7
Source dataset
uspto-grants-2012_05
Patent number
US08178672B2

Reaction notes

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