3-Fluoropentane-2,4-dione → 6-fluoro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carboxylic acid tert-butyl ester

HRID 1479004Notes

Reaction equation

HRID 1479004 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][C:14]2[C:10](=[N:11][NH:12][C:13]=2[NH2:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:17][CH:18]([C:22](=O)[CH3:23])[C:19](=O)[CH3:20]>CC(O)=O>[C:1]([O:5][C:6]([N:8]1[CH2:15][C:14]2=[C:13]3[N:12]([N:11]=[C:10]2[CH2:9]1)[C:22]([CH3:23])=[C:18]([F:17])[C:19]([CH3:20])=[N:16]3)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 116266523-Fluoropentane-2,4-dione2×HCID 178451527HCID 178451527, compound

Product 1

HCID 896503366-fluoro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carboxylic acid tert-butyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 3-amino-2,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester (4.3 g; 19.2 mmol; 1 eq.) and 3-fluoropentane-2,4-dione (2.49 g; 21.1 mmol; 1.1 eq.) in AcOH (40 mL) was stirred at room temperature for 18 hours. 3-fluoropentane-2,4-dione (0.45 g; 3.83 mmol; 0.2 eq.) was added and the reaction mixture was stirred for one hour then concentrated in vacuo. The residue was partitioned between EA and 1M NaOH and the aqueous layer extracted with EA. The combined organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (10 to 40% EA in cyclohexane) afforded the title compound (3 g, 58%) as a white solid. HPLC (max plot) 99.4%; Rt 3.83 min. UPLC/MS: (MS+) 307.2 ([M+H]+).

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was partitioned between EA and 1M NaOH
  3. extractionthe aqueous layer extracted with EA
  4. dry with materialThe combined organic phase was dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by column chromatography (10 to 40% EA in cyclohexane)

Sources & evidence

ORD record
ord-9b88b46a04b14eadb9af58848482b3bb
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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