Morpholine → 2-methyl-6-(4-morpholinyl)-4-nitro-1-(phenylmethyl)-1H-benzimidazole

HRID 2088602Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([N+:19]([O-:21])=[O:20])[C:5]2[N:9]=[C:8]([CH3:10])[N:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:18]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:10][C:8]1[N:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]2[CH:18]=[C:2]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:3]=[C:4]([N+:19]([O-:21])=[O:20])[C:5]=2[N:9]=1

Participants

Conditions

Temperature: 82 °C

Procedure

A mixture of 6-bromo-2-methyl-4-nitro-1-(phenylmethyl)-1H-benzimidazole (28 g), morpholine (21 g), Pd(dba)2 (4.6 g), Cs2CO3 (52.8 g) and X-Phos (3.9 g) in dioxane (250 mL) was degassed with nitrogen and then stirred at 82° C. for 4 h. The mixture was cooled to room temperature and the solvent was removed in-vacuo. The residue was then purified by silica gel chromatography eluted with EtOAc:petroleum ether=1:1 to afford the desired product as a yellow solid (17 g, 60%). 1H NMR (300 MHz, DMSO-d6): δ ppm 2.51 (s, 3H), 3.17 (t, 4H, J=4.8 Hz). 3.76 (t, 4H, J=4.8 Hz), 5.55 (s, 2H), 7.10-7.13 (m, 2H), 7.28-7.37 (m, 3H), 7.57-7.61 (m, 2H); LC-MS: m/e=353 [M+1]+.

Workup

customwas degassed with nitrogen
temperatureThe mixture was cooled to room temperature
customthe solvent was removed in-vacuo
customThe residue was then purified by silica gel chromatography
washeluted with EtOAc

Sources & evidence

ORD record: ord-bb2ff4564c6746c7a7316ffec3822ab8
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08435988B2

Reaction notes

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