Glycine → HCID 54721168, compound

HRID 598213Notes

Reaction equation

HRID 598213 reaction equation
[CH:1]1([CH2:4][CH2:5][N:6]2[C:11]3[N:12]=[CH:13][CH:14]=[CH:15][C:10]=3[C:9](=[O:16])O[C:7]2=[O:17])[CH2:3][CH2:2]1.C([C:20](CC)(C([O-])=O)[C:21]([O-])=[O:22])C.N12CCCN=C1CCCCC2.[NH2:40][CH2:41][C:42]([OH:44])=[O:43].[OH-].[Na+]>O.O1CCOCC1>[CH:1]1([CH2:4][CH2:5][N:6]2[C:11]3[C:10](=[CH:15][CH:14]=[CH:13][N:12]=3)[C:9]([OH:16])=[C:20]([C:21]([NH:40][CH2:41][C:42]([OH:44])=[O:43])=[O:22])[C:7]2=[O:17])[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 750GlycineHCID 14798Sodium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 69515632,2-DiethylpropanedioateHCID 10192716HCID 10192716, compound

Product 1

HCID 54721168HCID 54721168, compoundYield 2.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-(2-cyclopropylethyl)-2H-pyrido[2,3-d][1,3]oxazine-2,4 (1H)-dione (Prepared according to PCT Int. Appl. (2003), WO 2003059356 A2)(0.232 g, 1.00 mmol) and diethylmalonate (0.152 mL, 1.00 mmol) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (0.300 mL, 2.00 mmol). 1,4-dioxane (1.0 mL) was added and the solution was heated to 150° C. for 20 min. in a Biotage Initiator microwave synthesizer (http://www.biotage.com). Following cooling, glycine (0.113 g, 1.50 mmol) was added and the solution was heated to 200° C. for 20 min. in a Biotage Initiator microwave synthesizer. The reaction mixture was then cooled, treated with 6M aqueous sodium hydroxide (2.0 mL), diluted with water and extracted with diethyl ether. The aqueous layer was then acidified with 6M aqueous hydrochloric acid and extracted twice with ethyl acetate. The organic solution was dried over MgSO4, filtered, and concentrated in vacuo. The mixture was 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 white solid (0.008 g; 2.4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.0 (s, 1H), 10.5 (t, J=5.6 Hz, 1H), 8.83 (dd, J=4.5, 1.8 Hz, 1H), 8.46 (dd, J=8.0, 1.9 Hz, 1H), 7.43 (dd, J=8.0, 4.7 Hz, 1H), 4.41-4.60 (m, 2H), 4.13 (d, J=5.6 Hz, 2H), 1.55 (q, J=7.3 Hz, 2H), 0.67-0.82 (m, 1H), 0.32-0.41 (m, 2H), −0.09-0.04 (m, 2H). MS(ES+) m/e 332 [M+H]+.

Workup

  1. temperatureFollowing cooling
  2. temperaturethe solution was heated to 200° C. for 20 min. in a Biotage Initiator microwave synthesizer
  3. temperatureThe reaction mixture was then cooled
  4. extractionextracted with diethyl ether
  5. extractionextracted twice with ethyl acetate
  6. dry with materialThe organic solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe mixture was purified via preparative HPLC(YMC 75×30 mm column, 0.1% TFA in water and 0.1% TFA in acetonitrile)

Sources & evidence

ORD record
ord-83172967d482471980f1e9835e08563e
Source dataset
uspto-grants-2011_03
Patent number
US07897612B2

Reaction notes

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