Triethylamine → HCID 67778281, compound

HRID 1026299Notes

Reaction equation

HRID 1026299 reaction equation
Cl.[CH:2]1([CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[C:14]([CH:15]=2)=[N:13][N:12]([C:16]2[CH:26]=[CH:25][C:19]([O:20][CH2:21][C@@H:22]([NH2:24])[CH3:23])=[CH:18][CH:17]=2)[CH:11]=3)[CH2:4][CH2:3]1.[CH3:27][N:28]=[C:29]=[O:30].C(N(CC)CC)C>C1COCC1>[CH:2]1([CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[C:14]([CH:15]=2)=[N:13][N:12]([C:16]2[CH:26]=[CH:25][C:19]([O:20][CH2:21][C@@H:22]([NH:24][C:29]([NH:28][CH3:27])=[O:30])[CH3:23])=[CH:18][CH:17]=2)[CH:11]=3)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12228Methyl IsocyanateHCID 67777876HCID 67777876, compound

Product 1

HCID 67778281HCID 67778281, compoundYield 58.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of tert-butyl [(1S)-2-{4-[6-(cyclopropylmethoxy)-2H-indazol-2-yl]phenoxy}-1-methylethyl]carbamate (310 mg) and 4M hydrogen chloride/ethyl acetate (5 mL) was stirred at room temperature for 1 hr. To the reaction mixture was added diethyl ether, and the resultant precipitate was collected by filtration, and washed with ethyl acetate to give (2S)-1-{4-[6-(cyclopropylmethoxy)-2H-indazol-2-yl]phenoxy}propan-2-amine hydrochloride (255 mg). A mixture of (2S)-1-{4-[6-(cyclopropylmethoxy)-2H-indazol-2-yl]phenoxy}propan-2-amine hydrochloride (84 mg), methyl isocyanate (38.5 mg), triethylamine (68 mg) and THF (1 mL) was stirred at room temperature overnight. The solvent was evaporated under reduced pressure, and the residue was diluted with ethyl acetate, and the mixture was washed with water. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as colorless crystals (51.9 mg).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate
  3. washthe mixture was washed with water
  4. extractionThe separated aqueous layer was extracted again with ethyl acetate
  5. washThe combined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d77d1bd0436542048a479fccb7476e09
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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