Sodium ethoxide → HCID 57590667, compound

HRID 1783827Notes

Reaction equation

HRID 1783827 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][C:18]([F:21])=[C:17]([O:22][CH3:23])[CH:16]=1)=O.Cl.[NH2:26]/[C:27](/[NH:30][CH:31]1[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]1)=[N:28]/[H].[O-]CC.[Na+]>C(O)C>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:8]2[N:9]=[C:10]3[N:14]([C:7]=2[C:5]2[CH:4]=[CH:3][N:28]=[C:27]([NH:30][CH:31]4[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]4)[N:26]=2)[CH:13]=[CH:12][S:11]3)=[CH:16][C:17]=1[O:22][CH3:23]

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 68801242HCID 68801242, compoundHCID 178478973HCID 178478973, compound

Product 1

HCID 57590667HCID 57590667, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 3-(dimethylamino)-1-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]prop-2-en-1-one (0.537 g, 1.55 mmol) and tert-butyl 4-{[(Z)-amino(imino)methyl]amino}piperidine-1-carboxylate hydrochloride (0.650 g, 2.33 mmol) was diluted with 13 ml of absolute ethanol and treated with 1.35 eq. of a 21% w/w solution of sodium ethoxide in ethanol (780 μl) 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 50 ml of ethyl acetate and 50 ml of water. The phases were separated and the aqueous phase was extracted with 50 ml of ethyl acetate. The combined organic extracts were washed with 100 ml of water, and then with a saturated sodium chloride solution (100 ml). The organic phase was dried with sodium sulfate, filtered and concentrated in vacuo, to give a brown oil. The product was purified by flash chromatography on silica gel (gradient 50% to 75% ethyl acetate in hexanes) to yield 0.713 g of a pale yellow solid (88%). 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 8.71 (br. s, 1H), 8.11 (d, J=5.5 Hz, 1H), 7.45 (d, J=4.3 Hz, 1H), 7.35 (dd, J=8.2, 2.0 Hz, 1H), 7.26 (dd, J=11.3, 8.2 Hz, 1H), 7.19-7.12 (m, 2H), 6.39 (d, J=5.1 Hz, 1H), 3.98-3.87 (m, 3H), 3.83 (s, 3H), 2.91 (t, J=11.5 Hz, 2H), 1.94-1.87 (m, 2H), 1.47-1.35 (m, 2H), 1.42 (s, 9H). LCMS: 525 [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 50 ml of ethyl acetate
  7. washThe combined organic extracts were washed with 100 ml of water
  8. dry with materialThe organic phase was dried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a brown oil
  12. customThe product was purified by flash chromatography on silica gel (gradient 50% to 75% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9b4501613ebb4ca9b57b37a0651b562c
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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