tert-Butanol → 8-chloro-N-[(2-chloro-5-methoxyphenyl)sulfonyl]-3-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide

HRID 467828Notes

Reaction equation

HRID 467828 reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:12]([CH3:18])=[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.CN(C)CCCN=C=NCC.C(O)(C)(C)C.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][C:38]=1[S:45]([NH2:48])(=[O:47])=[O:46]>CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][C:2]1[C:3]2[N:4]([C:12]([CH3:18])=[C:13]([C:15]([NH:48][S:45]([C:38]3[CH:39]=[C:40]([O:43][CH3:44])[CH:41]=[CH:42][C:37]=3[Cl:36])(=[O:47])=[O:46])=[O:17])[N:14]=2)[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 3140422-Chloro-5-methoxybenzene-1-sulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 674949048-Chloro-3-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Product 1

HCID 674947338-chloro-N-[(2-chloro-5-methoxyphenyl)sulfonyl]-3-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamideYield 37.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To the carboxylic acid prepared in Step B (200 mg, 0.72 mmol) was added a solution of 4-(dimethylamino)pyridine (262 mg, 2.15 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (344 mg, 1.79 mmol) in a 1:1 solvent mixture of t-butanol (5 mL) and dichloromethane (5 mL). The reaction mixture was stirred for 15 minutes, 2-chloro-5-methoxybenzenesulfonamide (143 mg, 0.65 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 layers were combined, dried over magnesium sulfate, and concentrated under reduced pressure to afford a solid. The solid was rinsed with diethyl ether to afford 118 mg of the title compound, a compound of the present invention, as a white solid, m.p. 222-223° C. 1H NMR (dmso-d6) δ 10.0 (br s, 1H), 8.94 (s, 1H), 7.96 (s, 1H), 7.65 (d, 1H), 7.59 (d, 1H), 7.30 (dd, 1H), 3.87 (s, 3H) 2.71 (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 materialdried 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-b11e2ff4eded47738d396f18ec4f9413
Source dataset
uspto-grants-2014_01
Patent number
US08623890B2

Reaction notes

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