Lithium Hydroxide → 2-Tert-butoxy-2-[4-(2,4-dimethylphenyl)-7-[1-(2-hydroxyethyl)triazol-4-yl]-2-methyl-1-oxo-3-isoquinolyl]acetic acid

HRID 572533Notes

Reaction equation

HRID 572533 reaction equation
[C:1]([O:5][CH:6]([C:11]1[N:12]([CH3:32])[C:13](=[O:31])[C:14]2[C:19]([C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=1[CH3:28])=[CH:18][CH:17]=[C:16]([C:29]#[CH:30])[CH:15]=2)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].C([O:36][CH2:37][CH2:38][N:39]=[N+:40]=[N-:41])(=O)C.O=C1O[C@H]([C@H](CO)O)C(O)=C1O.[OH-].[Li+]>C(O)C.O.C(OCC)(=O)C.CO.O1CCCC1.O.S([O-])([O-])(=O)=O.[Cu+2]>[CH3:4][C:1]([O:5][CH:6]([C:11]1[N:12]([CH3:32])[C:13](=[O:31])[C:14]2[C:19]([C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=1[CH3:28])=[CH:18][CH:17]=[C:16]([C:29]1[N:41]=[N:40][N:39]([CH2:38][CH2:37][OH:36])[CH:30]=1)[CH:15]=2)[C:7]([OH:9])=[O:8])([CH3:2])[CH3:3]

Participants

11

Reactant 4

HCID 3939Lithium HydroxideHCID 120185192-Azidoethyl acetateHCID 54670067L-Ascorbic AcidHCID 86700725Methyl 2-(tert-butoxy)-2-(4-(2,4-dimethylphenyl)-7-ethynyl-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate

Product 1

HCID 715962962-Tert-butoxy-2-[4-(2,4-dimethylphenyl)-7-[1-(2-hydroxyethyl)triazol-4-yl]-2-methyl-1-oxo-3-isoquinolyl]acetic acid

Reagents, catalysts & solvents 6

HCID 61499Cupric sulfate monohydrateCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of methyl 2-(tert-butoxy)-2-(4-(2,4-dimethylphenyl)-7-ethynyl-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate (26.0 mg, 0.060 mmol), 2-azidoethyl acetate (10.11 mg, 0.078 mmol), ascorbic acid (2.123 mg, 0.012 mmol) and copper sulfate monohydrate (1.923 mg, 0.012 mmol) in Ethanol (1.2 mL) and Water (0.2 mL) was irradiated in the microwave at 120° C. for 10 minutes. The mixture was diluted with ethyl acetate, then washed with saturated sodium bicarbonate and brine. The organic phase was dried over sodium sulfate, filtered and concentrated. The resulting crude residue in methanol (1.0 mL), tetrahydrofuran (THF) (1.0 mL) and water (0.2 mL) was treated with lithium hydroxide (28.8 mg, 1.205 mmol) and then heated to 60° C. for 90 minutes. The mixture was concentrated to dryness, water was added and the mixture was adjusted to pH 3-4 with 1N hydrochloric acid. The mixture was extracted with ethyl acetate; the extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by reverse phase chromatography to afford the desired product as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) (atropisomers) δ=8.75-8.54 (m, 1 H), 8.14 (br. s., 2 H), 7.43 (d, J=7.6 Hz, 1 H), 7.15 (d, J=14.6 Hz, 2 H), 7.04-6.85 (m, 1 H), 5.44-5.15 (m, 1 H), 4.56 (m, 2 H), 4.14 (m, 2 H), 3.83-3.64 (m, 3 H), 2.43 (s, 3 H), 2.15-1.83 (m, 3 H), 1.29-0.97 (m, 9 H); LC/MS (m/z) ES+=505 (M+1).

Workup

  1. customwas irradiated in the microwave at 120° C. for 10 minutes
  2. washwashed with saturated sodium bicarbonate and brine
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. concentrationThe mixture was concentrated to dryness, water
  7. additionwas added
  8. extractionThe mixture was extracted with ethyl acetate
  9. washthe extracts were washed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-307a6aa1080f4d0ea4725fce8f491eae
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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