Hydrochloric Acid → Benzamide, 2-((5-chloro-2-((3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl)amino)-4-pyridinyl)amino)-N-methoxy-, hydrochloride (1:1)

HRID 1472541Notes

Reaction equation

HRID 1472541 reaction equation
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:29]=[CH:28][CH:27]=[CH:26][C:20]=2[C:21]([NH:23][O:24][CH3:25])=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1.Cl.C(OCC)C>C(OCC)(=O)C>[ClH:1].[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:29]=[CH:28][CH:27]=[CH:26][C:20]=2[C:21]([NH:23][O:24][CH3:25])=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:15])[CH3:16])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 46214930Gsk-2256098

Product 1

HCID 54589075Benzamide, 2-((5-chloro-2-((3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl)amino)-4-pyridinyl)amino)-N-methoxy-, hydrochloride (1:1)Yield 198.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
52.5 °C

Procedure

2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide (235.2 g total weight, 228.0 g assayed content, 549.5 mmoles) was slurried in ethyl acetate (7.1 L, 30 volumes). The mixture was heated to about 50-55° C. to afford a cloudy solution. The cloudy solution was filtered. To the filtered solution was added 2.0 M HCl in diethyl ether (210 g, 281 mL, 1.02 equiv.) over 15-20 minutes. Upon HCl addition, a white slurry was observed. It was stirred at room temperature for about 16-20 hours. Product was collected by filtration and rinsed with ethyl acetate (2×500 mL each). The wet cake was dried at 50-55° C./<5 mm Hg for 16-20 hours to a constant weight. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide, monohydrochloride, (245.9 g, 544.7 mmoles, 96% yield) was isolated as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 1.32 (d, J=6.57 Hz, 6 H) 2.18 (s, 3 H) 3.70 (s, 3 H) 4.35-4.62 (m, 1 H) 6.12 (br. s, 1 H) 6.60 (br. s, 1 H) 7.19-7.41 (m, 1 H) 7.48-7.75 (m, 3 H) 8.09 (s, 1 H) 9.59-9.99 (m, 2 H) 11.98 (br. s, 1 H). C18 HPLC RT=6.1 minutes (99.6% purity). MS (ESI): 414.8 [M+H]+.

Workup

  1. customto afford a cloudy solution
  2. filtrationThe cloudy solution was filtered
  3. filtrationProduct was collected by filtration
  4. washrinsed with ethyl acetate (2×500 mL each)
  5. customThe wet cake was dried at 50-55° C./<5 mm Hg for 16-20 hours to a constant weight

Sources & evidence

ORD record
ord-3be4967e775e47238bba332827627109
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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