Lithium Hydroxide → 2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid

HRID 1530364Notes

Reaction equation

HRID 1530364 reaction equation
C[O:2][C:3](=[O:36])[C:4]([N:7]1[CH2:12][CH2:11][CH:10]([S:13][C:14]2[CH:15]=[CH:16][C:17]3[O:26][CH2:25][CH2:24][N:23]4[C:19](=[N:20][C:21]([C:27]5[N:28]([CH:32]([CH3:34])[CH3:33])[N:29]=[CH:30][N:31]=5)=[CH:22]4)[C:18]=3[CH:35]=2)[CH2:9][CH2:8]1)([CH3:6])[CH3:5].[Li+].[OH-]>C1COCC1.O>[CH:32]([N:28]1[C:27]([C:21]2[N:20]=[C:19]3[N:23]([CH2:24][CH2:25][O:26][C:17]4[CH:16]=[CH:15][C:14]([S:13][CH:10]5[CH2:11][CH2:12][N:7]([C:4]([CH3:6])([CH3:5])[C:3]([OH:36])=[O:2])[CH2:8][CH2:9]5)=[CH:35][C:18]=43)[CH:22]=2)=[N:31][CH:30]=[N:29]1)([CH3:34])[CH3:33]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 683131132-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid methyl ester

Product 1

HCID 683131542-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid methyl ester (50 mg, 0.0979 mmol) in THF (4 mL) was added 1.0M LiOH in water (0.5 mL). The reaction mixture was first stirred at RT for 6 h, then left at RT for 7 days, and then heated at 120° C. for 1 h using microwave irradiation. Volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (C18, gradient 2-80% MeOH in H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH affording the title compound as a white solid (20 mg, 42%). LCMS: RT 2.45 min [M−H]+ 495.0.

Workup

  1. waitleft at RT for 7 days
  2. temperatureheated at 120° C. for 1 h
  3. custommicrowave irradiation
  4. customVolatiles were removed under reduced pressure
  5. customthe resulting residue was purified by column chromatography (C18, gradient 2-80% MeOH in H2O)
  6. washThe cartridge was washed with MeOH
  7. washthe product eluted with 2M NH3/MeOH affording the title compound as a white solid (20 mg, 42%)

Sources & evidence

ORD record
ord-19eee3db9fda4871847f87278f4442b3
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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