Sodium Hydroxide → 4-(4-bromo-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine

HRID 2088604Notes

Reaction equation

[CH3:1][C:2]1[N:6](CC2C=CC=CC=2)[C:5]2[CH:14]=[C:15]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[CH:16]=[C:17](N)[C:4]=2[N:3]=1.N([O-])=O.[Na+].[Na+].[Br-:30].[OH-].[Na+]>Br.O>[Br:30][C:17]1[C:4]2[N:3]=[C:2]([CH3:1])[NH:6][C:5]=2[CH:14]=[C:15]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH:16]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-methyl-6-(4-morpholinyl)-1-(phenylmethyl)-1H-benzimidazol-4-amine (2.3 g, 10 mmol) in aqueous HBr (50 mL) was added a solution of NaNO2 (720 mg, 10.5 mmol) in water (10 mL) dropwise at 0-5° C. After addition the mixture was stirred at 0° C. for 5 minutes, another solution of NaBr (3.1 g, 30 mmol) in aqueous HBr (50 mL) was added dropwise at 60° C. The resulting mixture was then heated to 80° C. for 30 minutes and then cooled to room temperature. It was neutralized with aqueous 2N NaOH and extracted with EtOAc (100 mL×3). The combined organic layers were concentrated in-vacuum and the residue was purified by silica gel chromatography eluted with petroleum ether:EtOAc=1:1 to give the desired product (1.7 g, 58%) as a white solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 2.44 (s, 3H), 3.07 (t, 4H, J=4.8 Hz), 3.74 (t, 4H, J=4.8 Hz), 6.85 (d, 1H, J=1.8 Hz), 7.04 (d, 1H, J=1.8 Hz), 12.20 (br s, 1H); LC-MS: m/e=296 [M+1]+

Workup

additionAfter addition the mixture
temperatureThe resulting mixture was then heated to 80° C. for 30 minutes
temperaturecooled to room temperature
extractionextracted with EtOAc (100 mL×3)
concentrationThe combined organic layers were concentrated in-vacuum
customthe residue was purified by silica gel chromatography
washeluted with petroleum ether

Sources & evidence

ORD record: ord-89a171d1f7da4d8cb4613d1776f81b67
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08435988B2

Reaction notes

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