Morpholine → (+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-morpholin-4-ylmethyl-isonicotinamide

Reaction equation

Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][N:28]=1)[C:6]([NH:8][C:9]1[S:10][C:11]2[C:17]([CH:18]3[CH2:23][O:22][CH2:21][CH2:20][O:19]3)=[CH:16][CH:15]=[C:14]([O:24][CH3:25])[C:12]=2[N:13]=1)=[O:7].C(=O)([O-])[O-].[Cs+].[Cs+].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[O:19]1[CH2:20][CH2:21][O:22][CH2:23][CH:18]1[C:17]1[C:11]2[S:10][C:9]([NH:8][C:6](=[O:7])[C:5]3[CH:26]=[CH:27][N:28]=[C:3]([CH2:2][N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[CH:4]=3)=[N:13][C:12]=2[C:14]([O:24][CH3:25])=[CH:15][CH:16]=1

Participants

Reactant 3

HCID 8083Morpholine

HCID 10796Cesium carbonate

HCID 22507718(+)-2-chloromethyl-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide

Product 1

HCID 22507728(+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-morpholin-4-ylmethyl-isonicotinamideYield 62%

Procedure

A suspension of 100 mg (0.24 mmol) (+)-2-chloromethyl-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide, 155 mg (0.48 mmol) cesium carbonate and 0.42 ml (4.76 mmol) morpholine was ultrasonicated at room temperature for 10 min. The reaction mixture was then concentrated in vacuo. Flash chromatography (1/1 acetone/hexane) followed by trituration in ether and hexane afforded 70 mg (62%) (+)-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-2-morpholin-4-ylmethyl-isonicotinamide as an off-white solid. [α]D20=+89.2° (c=0.49, CHCl3), ES-MS m/e (%): 471 (M+H+, 100).