Morpholine → 2-(4-Methoxy-phenyl)-5-morpholin-4-yl-oxazolo[5,4-b]pyridine

HRID 40718Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]2[O:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:10][C:5]2=[CH:4][CH:3]=1.[NH:19]1[CH2:26][CH2:25]C[C@H:20]1[C:21](O)=[O:22].N1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.O.[Cu]I>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[O:8][C:6]3[C:5]([N:10]=2)=[CH:4][CH:3]=[C:2]([N:19]2[CH2:20][CH2:21][O:22][CH2:25][CH2:26]2)[N:7]=3)=[CH:12][CH:13]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 5-chloro-2-(4-methoxy-phenyl)-oxazolo[5,4-b]pyridine (25 mg, 0.096 mmol) in DMSO (1 mL) was added L-proline (11.04 mg, 0.096 mmol), CuI (18.27 mg, 0.096 mmol), morpholine (13 μL, 0.15 mmol) and K3PO4 (40.7 mg, 0.192 mmol). The reaction vessel was sealed and heated to 90° C. overnight, at which point the reaction was diluted with water and extracted with EtOAc. The organics were concentrated leaving a residue that was purified by reverse phase chromatography to afford 2-(4-methoxy-phenyl)-5-morpholin-4-yl-oxazolo[5,4-b]pyridine (4.3 mg, 0.013 mmol, 14% yield). ES MS (M+H+)=312; 1H NMR (499 MHz, DMSO-d6): δ 8.07-8.02 (d, J=8.7 Hz, 2H); 7.98-7.94 (m, 1 H); 7.17-7.11 (d, J=8.7 Hz, 2H); 6.91 (d, J=8.8 Hz, 1H); 3.86 (s, 3H); 3.73 (t, J=4.8 Hz, 4H); 3.51 (t, J=4.8 Hz, 4H); HRMS m/z 312.1352 (C17H17N3O3+H+ requires 312.1343)

Workup

customThe reaction vessel was sealed
extractionextracted with EtOAc
concentrationThe organics were concentrated
customleaving a residue that
customwas purified by reverse phase chromatography

Sources & evidence

ORD record: ord-938f402e694a4575b24b0d7ef366bbb2
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530483B2

Reaction notes

Loading…