Triethylamine → 3-Cyano-5-hydroxymethyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-6-carboxylic Acid Ethyl Ester

HRID 1796600Notes

Reaction equation

HRID 1796600 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH2:18][OH:19])=[C:8]2[C:13](Cl)=[C:12]([C:15]#[N:16])[CH:11]=[N:10][N:9]2[CH:17]=1)=[O:5])[CH3:2].[O:20]([C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)CC)C>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH2:18][OH:19])=[C:8]2[C:13]([NH:31][C:30]3[CH:29]=[CH:28][C:27]([O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:33][CH:32]=3)=[C:12]([C:15]#[N:16])[CH:11]=[N:10][N:9]2[CH:17]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 8764(4-Aminophenoxy)benzeneHCID 207916274-Chloro-3-cyano-5-hydroxymethyl-pyrrolo[1,2-b]pyridazine-6-carboxylic Acid Ethyl Ester

Product 1

HCID 207916013-Cyano-5-hydroxymethyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-6-carboxylic Acid Ethyl EsterYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of compound 16B (84 mg, 0.30 mmol), 4-phenoxyaniline (72 mg, 0.39 mmol) and triethylamine (0.083 mL, 0.60 mmol) in THF (2.5 mL) was heated at 70° C. for 30 min. After cooled to room temperature, the reaction was concentrated to about 0.5 mL, diluted with MeOH (2 mL) and filtered. The solid was washed with MeOH and dried to give compound 16C as yellow solid (118 mg, 92%). HPLC: 92% at 2.12 min (retention time) (Prime Sphere 5u C18-HC column. 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm). MS (ES): m/z 429.0 [M+H]+.

Workup

  1. concentrationthe reaction was concentrated to about 0.5 mL
  2. additiondiluted with MeOH (2 mL)
  3. filtrationfiltered
  4. washThe solid was washed with MeOH
  5. customdried

Sources & evidence

ORD record
ord-f2cc6c7a9adf4adb9f14d7b13754ef82
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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