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

HRID 1028404Notes

Reaction equation

HRID 1028404 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.[CH2:35]([N:37]1[CH:41]=[C:40]([S:42]([NH2:45])(=[O:44])=[O:43])[C:39]([CH3:46])=[N:38]1)[CH3:36]>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:45][S:42]([C:40]3[C:39]([CH3:46])=[N:38][N:37]([CH2:35][CH3:36])[CH:41]=3)(=[O:43])=[O:44])=[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 196849831-ethyl-3-methyl-1H-pyrazole-4-sulfonamide2×

Product 1

HCID 498189648-chloro-N-[(1-ethyl-3-methyl-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-c]pyridine-2-carboxylic acid (63 mg, 0.24 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 (88 mg, 0.71 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (117 mg, 0.60 mmol). The reaction mixture was stirred for 15 min, after which time 1-ethyl-3-methyl-1H-pyrazole-4-sulfonamide (41 mg, 0.22 mmol, the product of Step A) was added, and the reaction mixture was stirred at room temperature overnight. Dichloromethane (100 mL) was added and the mixture was washed with 1 N hydrochloric acid (3×50 mL). The organic phase was separated, 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, filtered, and dried to afford 25 mg of the title compound, a compound of the present invention, as a solid, m.p. 189-190° C. 1H NMR (CDCl3) δ 9.85 (br s, 1H), 8.47 (s, 1H), 8.29 (s, 1H), 8.10 (s, 1H), 7.53 (s, 1H), 4.14 (q, 2H), 2.51 (s, 3H), 1.51 (t, 3H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. washthe mixture was washed with 1 N hydrochloric acid (3×50 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto afford a solid
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-9157f3e5813746fcaade73b43ffdc756
Source dataset
uspto-grants-2014_05
Patent number
US08735588B2

Reaction notes

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