Dimethylformamide → 7-[2-(4-Morpholinyl)ethoxy]-2-(4-nitrophenyl)imidazo[2,1-b]benzothiazole

HRID 71022Notes

Reaction equation

HRID 71022 reaction equation
CN(C=O)C.[N+:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]3[N:21]([CH:22]=2)[C:20]2[CH:23]=[CH:24][C:25]([OH:27])=[CH:26][C:19]=2[S:18]3)=[CH:11][CH:10]=1)([O-:8])=[O:7].C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>O>[N:38]1([CH2:37][CH2:36][O:27][C:25]2[CH:24]=[CH:23][C:20]3[N:21]4[CH:22]=[C:15]([C:12]5[CH:13]=[CH:14][C:9]([N+:6]([O-:8])=[O:7])=[CH:10][CH:11]=5)[N:16]=[C:17]4[S:18][C:19]=3[CH:26]=2)[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 299332572-(4-Nitrophenyl)imidazo[2,1-b]benzothiazol-7-ol

Product 1

HCID 445987167-[2-(4-Morpholinyl)ethoxy]-2-(4-nitrophenyl)imidazo[2,1-b]benzothiazoleYield 86%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

This product was prepared according to J. Med. Chem. 2009, 52, 7808-7816 with some modifications. A mixture of 2-amino-1,3-benzothiazol-6-ol (2.0 g, 12.18 mmol) and 2-bromo-4′-nitroacetophenone (2.97 g, 12.18 mmol) in IPA (40 ml) was heated to reflux for 24 h. The reaction mixture was then cooled to 0° C. and the resulting precipitate was filtrated and washed with IPA to afford 2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazol-7-ol (65% c.y.). To a DMF (52 ml) solution of 2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazol-7-ol was added potassium carbonate (2.94 g) and 4-(2-chloroethyl)morpholine hydrochloride (1.97 g). The reaction mixture was heated to 85° C. and stirred at the same temperature for 48 h. Then it was poured into water (100 ml), filtered and washed with water and ethyl ether to give 7-(2-morpholin-4-yl-ethoxy)-2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazole (86% c.y.). A mixture of 7-(2-morpholin-4-yl-ethoxy)-2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazole and ammonium chloride (0.77 g) in ethanol (50 ml) was heated to reflux, and then iron powder (3.0 g) was added. The mixture was refluxed for 5 h and then immediately filtered though Celite and washed with hot ethanol. The filtrate was concentrated, neutralized with saturated NaHCO3 solution and extracted with DCM. The organic solution was dried with Na2CO3 and the solvent was removed under reduced pressure to afford the desired product [4-(7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b]benzothiazol-2-yl]aniline (32% c.y.).

Workup

  1. filtrationfiltered
  2. washwashed with water and ethyl ether

Sources & evidence

ORD record
ord-4af641d4cd3c4b6fab664e5a12a77cb0
Source dataset
uspto-grants-2014_09
Patent number
US08822698B2

Reaction notes

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