4-Hydroxy-3-methyl-3-buten-2-one → 6,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carboxylic acid tert-butyl ester

HRID 1478994Notes

Reaction equation

HRID 1478994 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].O/[CH:18]=[C:19](\[CH3:23])/[C:20](=O)[CH3:21]>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:20]([CH3:21])=[C:19]([CH3:23])[CH:18]=[N:16]3)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 63817584-Hydroxy-3-methyl-3-buten-2-oneHCID 178451527HCID 178451527, compound

Product 1

HCID 896439196,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carboxylic acid tert-butyl esterYield 11%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 3-amino-2,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester (1 g; 4.46 mmol; 1 eq.) and (3E)-4-hydroxy-3-methylbut-3-en-2-one (prepared according to J. Het. Chem. 1980, 17(1), 33-37) (0.6 g; 4.91 mmol; 1.1 eq.) in AcOH (5 mL) was stirred at room temperature for 18 hours then concentrated in vacuo. The residue was partitioned between 1M NaOH and DCM, the organic layer was dried over magnesium sulfate and concentrated in vacuo. The resulting oil was triturated in Et2O, the precipitate filtered off and the solution concentrated in vacuo. The residue was purified by SFC (column: Chiralpak IC, eluent 25% MeOH) to afford successively the title compound (140 mg, 11%) as a white solid and Intermediate C2. 1H NMR (CDCl3) δ 8.33 (s, 1H), 4.72-4.62 (m, 4H), 2.54 (d, J=3.1 Hz, 3H), 2.29 (d, J=0.7 Hz, 3H), 1.52 (d, J=3.3 Hz, 9H). HPLC (max plot) 87.3%; Rt 3.27 min. UPLC/MS: (MS+) 289.1 ([M+H]+).

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was partitioned between 1M NaOH and DCM
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting oil was triturated in Et2O
  6. filtrationthe precipitate filtered off
  7. concentrationthe solution concentrated in vacuo
  8. customThe residue was purified by SFC (column: Chiralpak IC, eluent 25% MeOH)

Sources & evidence

ORD record
ord-7d36d0e25f4c4b2ea6006f013c5f30ec
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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