Hydrochloric Acid → HCID 118382894, compound

HRID 2202769Notes

Reaction equation

HRID 2202769 reaction equation
[Cl:1][C:2]1[C:3]([O:40]C)=[N:4][CH:5]=[C:6]([Cl:39])[C:7]=1[CH2:8][CH2:9][N:10]([CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:11]([C:13]1[CH:14]=[N:15][N:16]([C@H:22]2[CH2:27][CH2:26][C@H:25]([C:28]([O:30]CC)=[O:29])[C@H:24]([CH3:33])[CH2:23]2)[C:17]=1[C:18]([F:21])([F:20])[F:19])=[O:12].Cl>>[Cl:1][C:2]1[C:3](=[O:40])[NH:4][CH:5]=[C:6]([Cl:39])[C:7]=1[CH2:8][CH2:9][N:10]([CH2:34][C:35]([CH3:37])([CH3:36])[CH3:38])[C:11]([C:13]1[CH:14]=[N:15][N:16]([C@H:22]2[CH2:27][CH2:26][C@H:25]([C:28]([OH:30])=[O:29])[C@H:24]([CH3:33])[CH2:23]2)[C:17]=1[C:18]([F:21])([F:20])[F:19])=[O:12]

Participants

3

Reactant 2

HCID 313Hydrochloric Acid2×HCID 131735780HCID 131735780, compound

Product 1

HCID 118382894HCID 118382894, compoundYield 56%

Conditions

Temperature
120 °C

Procedure

(1S,2R,4S)-ethyl 4-(4-((2-(3,5-dichloro-2-methoxypyridin-4-yl)ethyl)(neopentyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2-methylcyclohexanecarboxylate (109 mg, 0.175 mmol) was treated with aqueous hydrochloric acid (5.0 N, 3.00 mL, 15.00 mmol) and hydrochloric acid (4.0 N in 1,4-dioxane, 3.00 mL, 12.00 mmol), fitted with a reflux condenser and heated to 120° C. for 3 h. The reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator) and the crude residue was purified on a Gilson (Gemini™ Phenomenex; 30×150 mm, 5 u, using a gradient of 10-95% 0.1% TFA/CH3CN in 0.1% TFA/water), concentrated in a genevac overnight affording (1S,2R,4S)-4-(4-((2-(3,5-dichloro-2-oxo-1,2-dihydropyridin-4-yl)ethyl)(neopentyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2-methylcyclohexanecarboxylic acid (57 mg, 0.098 mmol, 56% yield) as a white amorphous solid. MS (ESI) 579.0, 581.2 [M+H]+.

Workup

  1. customfitted with a reflux condenser
  2. concentrationThe reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator)
  3. customthe crude residue was purified on a Gilson (Gemini™ Phenomenex
  4. concentrationconcentrated in a genevac overnight

Sources & evidence

ORD record
ord-55a85805623f45e3bfb89fcc8026c45e
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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