1,2-Dichloroethane → 2-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)-N-hydroxy-N-methylbenzamide

HRID 62525

Reaction equation

HRID 62525 reaction equation
[Cl:1][C:2]1[C:3]([NH:17][C:18]2[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=2[C:20]([OH:22])=O)=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH2:14][CH3:15])[N:12]=[C:11]([CH3:16])[CH:10]=2)=[N:6][CH:7]=1.C1C=C[C:30]2[N:35]([OH:36])N=NC=2C=1.C(Cl)CCl.CNO.CCN(C(C)C)C(C)C>CN(C)C=O>[Cl:1][C:2]1[C:3]([NH:17][C:18]2[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=2[C:20]([N:35]([OH:36])[CH3:30])=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH2:14][CH3:15])[N:12]=[C:11]([CH3:16])[CH:10]=2)=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 11647MethylhydroxylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 593144602-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acid

Product 1

HCID 545889882-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)-N-hydroxy-N-methylbenzamideYield 23.05%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

A solution of 2-({5-chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acid (55 mg, 0.148 mmol), HOBT (22.65 mg, 0.148 mmol) and EDC (28.4 mg, 0.148 mmol) in N,N-dimethylformamide (DMF) (5 mL) was stirred under nitrogen at room temp for 30 minutes. To this solution was added N-methylhydroxylamine (12.35 mg, 0.148 mmol) and the solution was stirred for another 15 minutes. The reaction mixture was cooled to 5° C. and DIEA (0.052 mL, 0.296 mmol) was added dropwise. After addition, the reaction mixture was stirred at room temperature overnight. The reaction mixture was purified using preparative HPLC (0.1% formic acid, 5 to 95% water: acetonitrile). Fractions were combined and evaporated. 2-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)-N-hydroxy-N-methylbenzamide (16 mg, 0.034 mmol, 23.05% yield) isolated as a white solid. LCMS (M+H)+=401.0 (M+H); 1H NMR (400 MHz, MeOD) ppm 1.30 (t, J=7.20 Hz, 3 H) 2.19 (s, 3 H) 3.37 (d, J=1.52 Hz, 3 H) 3.96 (q, J=7.07 Hz, 2 H) 5.95 (s, 1 H) 6.32 (s, 1 H) 7.21-7.33 (m, 1 H) 7.42-7.53 (m, 2 H) 7.56 (d, J=7.33 Hz, 1 H) 7.86 (s, 1 H).

Workup

  1. additionAfter addition
  2. stirringthe reaction mixture was stirred at room temperature overnight
  3. customThe reaction mixture was purified
  4. customevaporated

Sources & evidence

ORD record
ord-46afd01249a44d29bdf1c2cf5c20339c
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Linked notes

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