tert-Butanol → 8-chloro-N-[(3-chloro-1-ethyl-1H-pyrazol-4-yl)sulfonyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide

HRID 467822Notes

Reaction equation

HRID 467822 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.C(O)(C)(C)C.Cl.CN(C)CCCN=C=NCC.[Cl:35][C:36]1[C:40]([S:41]([NH2:44])(=[O:43])=[O:42])=[CH:39][N:38]([CH2:45][CH3:46])[N:37]=1>CN(C)C1C=CN=CC=1.C(OCC)C.CCCCCC.ClCCl>[Cl:1][C:2]1[C:3]2[N:4]([CH:12]=[C:13]([C:15]([NH:44][S:41]([C:40]3[C:36]([Cl:35])=[N:37][N:38]([CH2:45][CH3:46])[CH:39]=3)(=[O:43])=[O:42])=[O:17])[N:14]=2)[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

9

Reactant 4

HCID 6386tert-ButanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 39288178-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acidHCID 666469323-chloro-1-ethyl-1H-pyrazole-4-sulfonamide2×

Product 1

HCID 498191158-chloro-N-[(3-chloro-1-ethyl-1H-pyrazol-4-yl)sulfonyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of 8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid (110 mg, 0.42 mmol, prepared as described in Example 1 Step C) in a 1:1 mixture of t-butanol (5 mL) and dichloromethane (5 mL) was added 4-(dimethylamino)pyridine (152 mg, 1.25 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (96 mg, 0.5 mmol). The reaction mixture was stirred for 15 min after which time 3-chloro-1-ethyl-1H-pyrazole-4-sulfonamide (81 mg, 0.38 mmol, the product of Step D) was added and stirring was continued at room temperature overnight. Dichloromethane (100 mL) was then added and the mixture was extracted with 1 N hydrochloric acid (3×50 mL). The separated organic phases were combined, dried over magnesium sulfate, and concentrated under reduced pressure to afford a solid. The solid was suspended in a mixture of diethyl ether and hexane and filtered to afford 85 mg of the title compound, a compound of the present invention, as a solid, m.p. 184-185° C. 1H NMR (CDCl3) δ 9.96 (br s, 1H), 8.47 (s, 1H), 8.29 (s, 1H), 8.16 (s, 1H), 7.54 (s, 1H), 4.17 (q, 2H), 1.54 (t, 3H).

Workup

  1. extractionthe mixture was extracted with 1 N hydrochloric acid (3×50 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford a solid
  5. filtrationfiltered

Sources & evidence

ORD record
ord-71e3630326fb4824b9679957e68b88b1
Source dataset
uspto-grants-2014_01
Patent number
US08623890B2

Reaction notes

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