2-(Chloromethyl)-5-ethyl-1,3,4-oxadiazole → (R)-2-chloro-5-((5-ethyl-1,3,4-oxadiazol-2-yl)methyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

HRID 2169550Notes

Reaction equation

HRID 2169550 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][CH2:7][C@@H:6]3[CH2:12][O:13][CH2:14][CH2:15][N:5]3[C:4]=2[N:3]=1.CC(C)([O-])C.[Na+].Cl[CH2:23][C:24]1[O:25][C:26]([CH2:29][CH3:30])=[N:27][N:28]=1>CS(C)=O.CCOC(C)=O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:23][C:24]3[O:25][C:26]([CH2:29][CH3:30])=[N:27][N:28]=3)[CH2:7][C@@H:6]3[CH2:12][O:13][CH2:14][CH2:15][N:5]3[C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 162273192-(Chloromethyl)-5-ethyl-1,3,4-oxadiazoleHCID 23676156Sodium t-butoxideHCID 86670088(R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

Product 1

HCID 86670098(R)-2-chloro-5-((5-ethyl-1,3,4-oxadiazol-2-yl)methyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridineYield 56%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 50 mL round-bottom flask was added (R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x3, 200 mg, 0.882 mmol) in DMSO (8 mL) followed by sodium tert-butoxide (102 mg, 1.059 mmol). The reaction mixture was stirred at room temperature for 10 minutes. 2-(Chloromethyl)-5-ethyl-1,3,4-oxadiazole (155 mg, 1.059 mmol) was then added to give an orange solution. After 1 hour, LC/MS indicated the reaction was complete. The reaction mixture was subsequently diluted with EtOAc and washed with aqueous saturated NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography (12 g SiO2 column, EtOAc(20-80%)hexane gradient) to give the title compound as a pale yellow solid (165 mg, 56%). 1H NMR (400 MHz, DMSO-d6) δ 1.24 (t, J=7.58 Hz, 3 H), 2.83 (d, J=7.33 Hz, 2 H), 2.93-3.03 (m, 1 H), 3.04-3.21 (m, 2 H), 3.36-3.51 (m, 2 H), 3.59-3.71 (m, 1 H), 3.85-3.98 (m, 2 H), 4.20-4.29 (m, 1 H), 4.57-4.67 (m, 1 H), 4.84-4.94 (m, 1 H), 7.57 (s, 1 H). ESI-MS m/z [M+H]+ calc'd for C14H17ClN6O2, 337.78; found 337.2.

Workup

  1. customto give an orange solution
  2. waitAfter 1 hour
  3. washwashed with aqueous saturated NH4Cl (3×)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by column chromatography (12 g SiO2 column, EtOAc(20-80%)hexane gradient)

Sources & evidence

ORD record
ord-8cfbd4b0f3f34b84bada31901ec79cc8
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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