Cyclopentanecarboxylic acid → HCID 25230807, compound

HRID 657590Notes

Reaction equation

HRID 657590 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:22]2[C:27](=[O:28])[NH:26][C:25](=[O:29])[C:24]([C:30]#[N:31])=[N:23]2)[CH:5]=[C:6]([Cl:21])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[N:11]([CH2:19]Cl)[N:10]=1.[CH:32]1([C:37]([OH:39])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33]1>C(#N)C.[Ag-]=O>[Cl:21][C:6]1[CH:5]=[C:4]([N:22]2[C:27](=[O:28])[NH:26][C:25](=[O:29])[C:24]([C:30]#[N:31])=[N:23]2)[CH:3]=[C:2]([Cl:1])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:16])[CH3:17])[C:12](=[O:18])[N:11]([CH2:19][O:39][C:37]([CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)=[O:38])[N:10]=1

Participants

5

Reactant 2

HCID 18840Cyclopentanecarboxylic acidHCID 57624577HCID 57624577, compound

Product 1

HCID 25230807HCID 25230807, compoundYield 21.1%

Reagents, catalysts & solvents 2

HCID 178418778HCID 178418778, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-[3,5-dichloro-4-(1-chloromethyl-5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (0.64 mmol) in acetonitrile (18 mL) at 25° C. was treated with cyclopentanecarboxylic acid (73.4 μL, 0.67 mmol) followed by silver (I) oxide (155.4 mg, 0.67 mmol). The reaction mixture was stirred at 25° C. in the dark for 3 d. At this time, the reaction was filtered through a pad of celite® and was rinsed with a solution of 90/10 methylene chloride/methanol (1×100 mL). The filtrate was then concentrated in vacuo. Biotage flash chromatography (40S, 0.5-1.25% methanol/methylene chloride) followed by reverse phase chromatography (Pursuit C-18 column, acetonitrile gradient with trifluoroacetic acid) followed by lyophilization afforded cyclopentanecarboxylic acid 3-[2,6-dichloro-4-(6-cyano-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-5-isopropyl-6-oxo-6H-pyridazin-1-ylmethyl ester (75.7 mg, 21%) as an off-white solid. ES+-HRMS m/e calcd for C24H22N6O6Cl2 (M+Na+) 583.0870, found 583.0871.

Workup

  1. filtrationAt this time, the reaction was filtered through a pad of celite®
  2. washwas rinsed with a solution of 90/10 methylene chloride/methanol (1×100 mL)
  3. concentrationThe filtrate was then concentrated in vacuo

Sources & evidence

ORD record
ord-cdb25ce46f1948bc968b4ba0deaa4b10
Source dataset
uspto-grants-2011_12
Patent number
US08076334B2

Reaction notes

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