Morpholine → 1-(4-Chlorophenyl)-3-(4-morpholin-4-ylbutyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

HRID 1818773Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH2:8][CH2:9][CH2:10][CH2:11][N:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[S:13]1(=[O:29])=[O:28]>>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([N:14]2[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:12]([CH2:11][CH2:10][CH2:9][CH2:8][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[S:13]2(=[O:28])=[O:29])=[CH:22][CH:23]=1

Participants

Reactant 2

HCID 8083Morpholine

HCID 578862331-(4-Bromobutyl)-3-(4-chlorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

Product 1

HCID 249367531-(4-Chlorophenyl)-3-(4-morpholin-4-ylbutyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxideYield 78%

Procedure

Morpholine (2 mL, 23 mmol) was added to a round bottom flask containing (50 mg, 0.12 mmol) of 1-(4-bromobutyl)-3-(4-chlorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (made in general procedure IV). The reaction flask was covered with a septum and stirred overnight at room temperature. The reaction solution was concentrated in vacuo and the crude product was pre-adsorbed onto Celite and purified via Isco chromatography (Redisep, silica, gradient 1-8% methanol in dichloromethane with ammonia) to afford 29 mg (78%) of 1-(4-chlorophenyl)-3-(4-morpholin-4-ylbutyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide. HPLC purity 100.0% at 210-370 nm, 8.2 minutes Xterra RP18, 3.5 u, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (ammonium formate buffer pH=3.5, acetonitrile/MeOH) for 10 minutes, hold 4 minutes.

Workup

concentrationThe reaction solution was concentrated in vacuo
custompurified via Isco chromatography (Redisep, silica, gradient 1-8% methanol in dichloromethane with ammonia)

Sources & evidence

ORD record: ord-0439d65bd24e4d4db1f98aa2c02ffc64
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07601722B2

Reaction notes

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