2-Chloro-5-methoxybenzene-1-sulfonamide → Fluazaindolizine

HRID 1028397Notes

Reaction equation

HRID 1028397 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([CH:12]=[C:13]([C:15]([OH:17])=O)[N:14]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[S:27]([NH2:30])(=[O:29])=[O:28]>CN(C)C1C=CN=CC=1.C(O)(C)(C)C.ClCCl>[Cl:1][C:2]1[C:3]2[N:4]([CH:12]=[C:13]([C:15]([NH:30][S:27]([C:20]3[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:19]=3[Cl:18])(=[O:29])=[O:28])=[O:17])[N:14]=2)[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

6

Reactant 2

HCID 3140422-Chloro-5-methoxybenzene-1-sulfonamideHCID 39288178-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Product 1

HCID 46944253FluazaindolizineYield 59.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 6386tert-ButanolSolvent

Procedure

To the carboxylic acid from Step C (243 mg, 0.92 mmol) was added a solution of 4-(dimethylamino)pyridine (340 mg, 2.76 mmol) and 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (232 mg, 2.3 mmol) in t-butanol (5 mL) and dichloromethane (5 mL). The reaction mixture was stirred for 15 min, 2-chloro-5-methoxybenzenesulfonamide (190 mg, 0.86 mmol) was added, and the reaction mixture was stirred at room temperature overnight. Dichloromethane (200 mL) was then added, the mixture was extracted with 1 N hydrochloric acid (3×100 mL), and the separated organic phase was dried over magnesium sulfate and concentrated under reduced pressure to afford a solid. The solid was rinsed with diethyl ether to afford 240 mg of the title compound, a compound of the present invention, as a white solid, m.p. 211-212° C. 1H NMR (CDCl3) δ 10.10 (br s, 1H), 8.46 (s, 1H), 8.27 (s, 1H), 7.86 (d, 1H), 7.54 (s, 1H), 7.38 (d, 1H), 7.09 (dd, 1H) 3.91 (s, 3H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with 1 N hydrochloric acid (3×100 mL)
  3. dry with materialthe separated organic phase was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto afford a solid
  6. washThe solid was rinsed with diethyl ether

Sources & evidence

ORD record
ord-af60f2add3154056b01e292da8cf194c
Source dataset
uspto-grants-2014_05
Patent number
US08735588B2

Reaction notes

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