Methanol → 6-[4-(4-Cyanophenyl)-7-ethyl-2-methylpyrrolo[1,2-b]pyridazin-3-yl]hexanoic acid

HRID 2250584Notes

Reaction equation

HRID 2250584 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]3[N:11]([C:26]([CH2:29][CH3:30])=[CH:27][CH:28]=3)[N:12]=[C:13]([CH3:25])[C:14]=2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([O:22]CC)=[O:21])=[CH:5][CH:4]=1)#[N:2].[OH-].[K+].CO>O1CCCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:10]3[N:11]([C:26]([CH2:29][CH3:30])=[CH:27][CH:28]=3)[N:12]=[C:13]([CH3:25])[C:14]=2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[CH:7][CH:8]=1)#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 11961741HCID 11961741, compound

Product 1

HCID 688045686-[4-(4-Cyanophenyl)-7-ethyl-2-methylpyrrolo[1,2-b]pyridazin-3-yl]hexanoic acidYield 4.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 6-[4-(4-cyanophenyl)-7-ethyl-2-methylpyrrolo[1,2-b]pyridazin-3-yl]hexanoate (15 g) in tetrahydrofuran (15 ml) was added 2N potassium hydroxide (7.4 ml), followed by methanol (7.4 ml). After stirring at 50° C. for 2 hours and 60° C. for 3 hours, the mixture was partitioned between 1N hydrochloric acid and ethyl acetate. The precipitates were filtered and washed with ethyl acetate. The organic layer and the washings were combined, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was triturated with ethyl acetate and the precipitates were filtered. The filtrate was purified by silica gel column chromatography eluting with a mixture of ethyl acetate and hexane (1:1) and triturated with isopropyl ether to give 6-[4-(4-cyanophenyl)-7-ethyl-2-methylpyrrolo[1,2-b]pyridazin-3-yl]hexanoic acid (650 mg) as an yellow crystals. The two precipitates were combined and recrystallized from ethyl acetate to give 6-{4-[4-(aminocarbonyl)phenyl]-7-ethyl-2-methylpyrrolo[1,2-b]pyridazin-3-yl}hexanoic acid (550 mg, 37.6%) as an yellow crystals.

Workup

  1. customthe mixture was partitioned between 1N hydrochloric acid and ethyl acetate
  2. filtrationThe precipitates were filtered
  3. washwashed with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. customThe residue was triturated with ethyl acetate
  8. filtrationthe precipitates were filtered
  9. customThe filtrate was purified by silica gel column chromatography
  10. washeluting with a mixture of ethyl acetate and hexane (1:1)
  11. customtriturated with isopropyl ether

Sources & evidence

ORD record
ord-543e8cd212a742f0a10f7fc5ff90891c
Source dataset
uspto-grants-2008_01
Patent number
US07317009B2

Reaction notes

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