Hydrochloric Acid → HCID 20789100, compound

HRID 1353818Notes

Reaction equation

HRID 1353818 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.O.[OH-].[Li+].C[NH:54]N(CC)NC.O.ON1C2C=CC=CC=2N=N1.Cl.[CH3:72][N:73]([CH3:82])[CH2:74][CH2:75]CN=C=NCC.Cl.C(=O)(O)[O-].[Na+]>O1CCOCC1.O1CCCC1.O1CCCC1.O>[NH:17]1[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:54][CH2:75][CH2:74][N:73]([CH3:72])[CH3:82])=[O:44])[CH:47]=[CH:48][CH:49]=2)=[N:20][CH:19]=[N:18]1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22479977HCID 22479977, compoundHCID 57041336N,N-Dimethylaminoethylamine

Product 1

HCID 20789100HCID 20789100, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of methyl 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl) (1,2,4-triazol-3-yl)]-1H-indazol-3-yl}benzoate (0.400 g, 0.619 mmol) in a tetrahydrofuran/water mixture (2.50 mL/1.00 mL) was added lithium hydroxide monohydrate (0.0780 g, 1.86 mmol) and the mixture heated at 60° C. for 21 h. To this mixture was added tetrahydrofuran (2.00 mL), N,N-dimethylaminoethyl amine (0.204 mL, 1.86 mmol), 1-hydroxybenzotriazole hydrate (0.251 g, 1.86 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.356 g, 1.86 mmol). This mixture was stirred for 18 h at ambient temperature. To this solution was added 6.0 M hydrochloric acid in dioxane (25.0 mL) and the mixture stirred at ambient temperature for 24 h. The mixture was cooled and poured into saturated aqueous sodium bicarbonate (50 mL). The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated. Addition of ethyl acetate (5 mL) initiated crystal growth and the ethyl acetate phase was pipetted off. The crystals were filtered. Purification by preparative HPLC (30–80% acetonitrile/water) followed by washing with saturated sodium bicarbonate and extraction with ethyl acetate gave the title compound (0.0719 g, 31% yield). 1H NMR (CD3OD) δ 8.82 (m, 1H), 8.51 (t, 1H), 8.36 (s, 1H), 8.22 (dt, 1H), 8.14 (dd, 1H), 7.93 (dt, 1H), 7.72 (dd, 1H), 7.67 (t, 1H), 3.59 (t, 2H), 2.65 (t, 2H), 2.35 (s, 6H). ES-MS (m/z) 376 [M+1]+

Workup

  1. stirringthe mixture stirred at ambient temperature for 24 h
  2. temperatureThe mixture was cooled
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic extracts were washed with saturated sodium bicarbonate
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. additionAddition of ethyl acetate (5 mL)
  9. filtrationThe crystals were filtered
  10. customPurification by preparative HPLC (30–80% acetonitrile/water)
  11. washby washing with saturated sodium bicarbonate and extraction with ethyl acetate

Sources & evidence

ORD record
ord-acb3a02c84504631a0036d83134a38bb
Source dataset
uspto-grants-2007_05
Patent number
US07220771B2

Reaction notes

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