Glycine → HCID 54721171, compound

HRID 598214Notes

Reaction equation

HRID 598214 reaction equation
C(N([CH2:6][CH3:7])CC)C.[CH2:8]([CH:10]([C:14](Cl)=[O:15])[C:11](Cl)=[O:12])[CH3:9].[O-:17]CC.[Na+].[N:21]12[CH2:31][CH2:30][CH2:29][N:28]=[C:27]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2.[NH2:32][CH2:33][C:34]([OH:36])=[O:35]>ClCCl.C(O)C.O>[OH:17][C:8]1[C:9]2[C:27](=[N:28][CH:29]=[CH:30][CH:31]=2)[N:21]([CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:7][CH:6]=2)[C:11](=[O:12])[C:10]=1[C:14]([NH:32][CH2:33][C:34]([OH:36])=[O:35])=[O:15]

Participants

9

Reactant 5

HCID 750GlycineHCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2723922Sodium ethoxideHCID 109209242-Ethylpropanedioyl dichloride

Product 1

HCID 54721171HCID 54721171, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of the compound from Example 4a) (0.480 g, 1.89 mmol) in dichloromethane (20.0 mL) was treated with triethylamine (0.410 mL, 2.97 mmol) followed by ethyl malonyl chloride (0.370 mL, 2.97 mmol). The mixture was stirred at ambient temperature for 1.5 h, followed by addition of water, and extraction twice with dichloromethane. The combined organic portions were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in ethanol (2.0 mL) and treated with sodium ethoxide (0.880 mL, 2.27 mmol, 21% solution in ethanol) at ambient temperature and stirred for 3 h. The solution was concentrated in vacuo and treated with water and 1N aqueous hydrochloric acid. The resulting solid was filtered, washed with water, and dried in vacuo. A solution of this solid (0.533 g, 1.60 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL, 1.60 mmol) and glycine (0.12 g, 1.60 mmol) in ethanol (3.0 mL) was heated to 180° C. for 30 min. in a Biotage Initiator microwave synthesizer. The solution was concentrated in vacuo and purified via preparative HPLC(YMC 75×30 mm column, 0.1% TFA in water and 0.1% TFA in acetonitrile) to afford the title compound as a light orange solid (0.113 g, 20%). 1H NMR (400 MHz, METHANOL-d4) δ ppm 13.0 (br. S., 1H), 10.5 (t, J=5.6 Hz, 1H), 8.80 (dd, J=4.5, 1.8 Hz, 1H), 8.57 (dd, J=7.8, 1.8 Hz, 1H), 7.44 (dd, J=8.0, 4.7 Hz, 1H), 7.17-7.41 (m, 5H), 5.77 (s, 2H), 4.24 (d, J=5.3 Hz, 2H). MS(ES+) m/e 354 [M+H]+.

Workup

  1. dry with materialThe combined organic portions were dried over magnesium sulfate
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in ethanol (2.0 mL)
  5. stirringstirred for 3 h
  6. concentrationThe solution was concentrated in vacuo
  7. additiontreated with water and 1N aqueous hydrochloric acid
  8. filtrationThe resulting solid was filtered
  9. washwashed with water
  10. customdried in vacuo
  11. concentrationThe solution was concentrated in vacuo
  12. custompurified via preparative HPLC(YMC 75×30 mm column, 0.1% TFA in water and 0.1% TFA in acetonitrile)

Sources & evidence

ORD record
ord-ae0f6b71ff574950830ea241e13c9816
Source dataset
uspto-grants-2011_03
Patent number
US07897612B2

Reaction notes

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