Sodium ethoxide → 6-Cyano-4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester

HRID 730535Notes

Reaction equation

CO[C:3]([C:5]1[N:6]([N:12]([C:18](=[O:25])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:7]=[C:8]([C:10]#[N:11])[CH:9]=1)=[O:4].[O-]CC.[Na+]>C(O)C>[CH2:23]([O:22][C:20]([C:19]1[C:18](=[O:25])[N:12]([CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[N:6]2[CH:7]=[C:8]([C:10]#[N:11])[CH:9]=[C:5]2[C:3]=1[OH:4])=[O:21])[CH3:24]

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of crude 4-cyano-1-[(2-ethoxycarbonyl-acetyl)-(3-methyl-butyl)-amino]-1H-pyrrole-2-carboxylic acid methyl ester (Example 15d, 2.552 mmol) in ethanol (30 mL) was added a 21% solution of sodium ethoxide in ethanol (2.07 g, 6.380 mmol) and the mixture was heated at 40° C. for 16 h. Upon cooling, the mixture was quenched with 1.0 M aqueous hydrochloric acid solution and brine. The aqueous mixture was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford the crude desired product, 6-cyano-4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester as a yellow solid, which was used in the next step without further purification. LC-MS (ESI) calcd for C16H19N3O4 317.14, found 318.3 [M+H+]. FT-IR (ATR) νmax (neat): 2231, 1642, 1610 cm−1.

Workup

temperatureUpon cooling
customthe mixture was quenched with 1.0 M aqueous hydrochloric acid solution and brine
extractionThe aqueous mixture was extracted with ethyl acetate
dry with materialthe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-74fa406ba4824e7ebc8185db07596582
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582754B2

Reaction notes

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