Hydrochloric Acid → HCID 178517703, compound

HRID 869154Notes

Reaction equation

HRID 869154 reaction equation
[F:1][C:2]1[C:3]([C:8]2([CH2:12][NH:13][C:14]3[N:15]=[N:16][C:17]([C:20]4[C:21]([O:26]C)=[N:22][CH:23]=[CH:24][CH:25]=4)=[CH:18][CH:19]=3)[CH2:11][CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl>CO>[F:1][C:2]1[C:3]([C:8]2([CH2:12][NH:13][C:14]3[N:15]=[N:16][C:17]([C:20]4[C:21]([OH:26])=[N:22][CH:23]=[CH:24][CH:25]=4)=[CH:18][CH:19]=3)[CH2:11][CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67453616HCID 67453616, compound

Product 1

HCID 178517703HCID 178517703, compoundYield 96.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a 50 mL round bottom flask was added N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)-6-(2-methoxypyridin-3-yl)pyridazin-3-amine (1.7 g, 4.7 mmol), concentrated hydrochloric acid (15 mL), and methanol (15 mL). The reaction was heated to 90° C. and stirred for 12 h. The reaction was concentrated, brought to pH of 11 through the addition of saturated potassium carbonate (20 mL), and then diluted with ethyl acetate (50 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and washed with lithium chloride (1×20 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated to give 3-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)pyridin-2-ol (1.6 g, 95%) as a tan powder. The isolated product (1.3 g, 3.7 mmol, 1.0 equiv) was transferred to a 100 mL round bottom flask, followed by the addition of a mixture of phosphorous oxytrichloride (24 mL) and DMF (8 mL). The reaction was heated to 90° C. and stirred for 6 h. The reaction was concentrated and carefully quenched with a 50% mixture of saturated sodium bicarbonate and lithium chloride until gas evolution ceased. The mixture was extracted with ethyl acetate (100 mL). The combined organic layers were then dried over Na2SO4, filtered, concentrated, and purified by silica gel column chromatography to give 1.2 g (88%) of 6-(2-chloropyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine as an off-white solid.

Workup

  1. concentrationThe reaction was concentrated
  2. additionbrought to pH of 11 through the addition of saturated potassium carbonate (20 mL)
  3. additiondiluted with ethyl acetate (50 mL)
  4. customAfter transferring to a separatory funnel
  5. stirringshaking
  6. customthe organic layer was separated from the aqueous layer
  7. washwashed with lithium chloride (1×20 mL)
  8. dry with materialThe organic layer was then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a4106bea417d4fb199ef04adeebf8694
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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