Lithium Hydroxide → HCID 178495990, compound

HRID 1353943Notes

Reaction equation

HRID 1353943 reaction equation
O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([CH:47]=[CH:48][CH:49]=2)[C:43](OC)=[O:44])=[N:8]1.[OH-].[Li+].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:74][O:75][CH2:76][CH2:77][NH2:78]>O1CCCC1.O.C(OCC)(=O)C.Cl.O1CCOCC1>[NH:18]1[CH:19]=[N:20][C:16]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[NH:7][N:8]=[C:9]3[C:40]2[CH:41]=[C:42]([C:43]([NH:78][CH2:77][CH2:76][O:75][CH3:74])=[O:44])[CH:47]=[CH:48][CH:49]=2)=[N:17]1

Participants

11

Reactant 5

HCID 3939Lithium HydroxideHCID 80182-MethoxyethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22479977HCID 22479977, compound

Product 1

HCID 178495990HCID 178495990, compoundYield 9%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

The title compound was prepared by dissolving methyl 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}benzoate (0.403 g, 0.62 mmol) and lithium hydroxide (0.052 g, 2.17 mmol) in tetrahydrofuran (3 mL) and water (2 mL). This reaction mixture was heated to 50° C. reacted overnight. The reaction was monitored by thin layer cluomatography (100% ethyl acetate). To this reaction, 1-hydroxybenzotriazole (0.256 g, 1.89 mmol), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.369 g, 1.92 mmol), and 2-methoxyethylamine (0.16 mL, 1.87 mmol) were added and allowed to stir overnight at room temperature. The reaction was then diluted with ethyl acetate and washed with a 1:1 solution of sodium chloride (saturated aqueous): sodium bicarbonate (saturated aqueous) and partitioned. The aqueous layer was extracted with ethyl acetate (2×), and the organic layers were combined, dried with sodium sulfate, filtered, and condensed. The crude solid was subsequently taken up in 4 N hydrochloride solution in dioxane (8 mL), and stirred at 50° C. overnight. The reaction was quenched by adding the mixture dropwise to sodium bicarbonate (saturated aqueous) (100 mL). The mixture was then extracted with ethyl acetate (3×), and the organics combined, dried with sodium sulfate, filtered, and condensed. The compound was purified by preparative HPLC (10–80% acetonitrile in H2O, 20 min.) (0.019 g, 9% yield): 1H NMR (CD3OD) δ 8.74 (s, 1H), 8.41 (t, 1H), 8.25 (br s, 1H), 8.15 (dt, 1H), 8.07 (d, 1H), 7.86 (dt, 1H), 7.63 (dd, 2H), 3.58 (s, 4H), 3.35 (s, 3H); ES-MS (m/z) 363 [M+1]+.

Workup

  1. customreacted overnight
  2. additionwere added
  3. washwashed with a 1:1 solution of sodium chloride (saturated aqueous)
  4. customsodium bicarbonate (saturated aqueous) and partitioned
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. customcondensed
  9. stirringstirred at 50° C. overnight
  10. customThe reaction was quenched
  11. additionby adding the mixture dropwise to sodium bicarbonate (saturated aqueous) (100 mL)
  12. extractionThe mixture was then extracted with ethyl acetate (3×)
  13. dry with materialdried with sodium sulfate
  14. filtrationfiltered
  15. customcondensed
  16. customThe compound was purified by preparative HPLC (10–80% acetonitrile in H2O, 20 min.) (0.019 g, 9% yield)

Sources & evidence

ORD record
ord-d984ff5a33744cabbd9a92d19e48c931
Source dataset
uspto-grants-2007_05
Patent number
US07220771B2

Reaction notes

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