1,2-Dichloroethane → 5-Chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide

HRID 1472582Notes

Reaction equation

HRID 1472582 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[C:22]([CH3:28])[CH:21]=3)[CH:13]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C1C=CC2[N:37]([OH:38])N=NC=2C=1.[CH2:39](Cl)CCl.CCN(C(C)C)C(C)C>CN(C)C=O.C(O)(=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[C:22]([CH3:28])[CH:21]=3)[CH:13]=2)=[C:6]([CH:10]=1)[C:7]([NH:37][O:38][CH3:39])=[O:9]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66769488HCID 66769488, compound

Product 1

HCID 593144635-Chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamideYield 26.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid (830 mg, 1.975 mmol) in N,N-dimethylformamide (20 mL) was added HOBT (363 mg, 2.370 mmol) and EDC (454 mg, 2.370 mmol) and the reaction mixture was stirred for 30 min. To this solution was added o-methoxylamine hydrochloride (198 mg, 2.370 mmol) and after 30 min the mixture was cooled to 0° C. DIEA (1.032 mL, 5.92 mmol) was added. The reaction mixture was stirred at the room temperature over the weekend. Water (100 mL) was added followed by acetic acid (1 mL) and the solution extracted with 2×50 ml of ethyl acetate. The organic layer was washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The product was purified by flash column chromatography on silica gel using EtOAc:DCM (10% to 100%). 5-Chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide (250 mg, 0.529 mmol, 26.8% yield) was isolated as a white foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.27 (d, J=6.57 Hz, 6 H) 2.11 (s, 3 H) 3.71 (s, 3 H) 4.20-4.55 (m, 1 H) 5.94 (s, 1 H) 6.63 (s, 1 H) 7.59 (s, 2 H) 7.67 (s, 1 H) 7.99 (s, 1 H) 8.50 (s, 1 H) 9.43 (br. s., 1 H) 12.03 (br. s., 1 H); HPLC Rt=2.46 min, MS (ESI): 449.1, 451.1 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred at the room temperature over the weekend
  2. extractionthe solution extracted with 2×50 ml of ethyl acetate
  3. washThe organic layer was washed with 2×50 ml
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe product was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-500ec50098324fd69ec4c7fce15981ca
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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