Sodium Hydroxide → 2-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-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 1530378Notes

Reaction equation

HRID 1530378 reaction equation
C[O:2][C:3](=[O:38])[C:4]([N:7]1[CH2:12][CH2:11][CH:10]([S:13][C:14]2[C:15]([F:37])=[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:33]([CH3:35])[CH3:34])[N:29]=[C:30]([CH3:32])[N:31]=5)=[CH:22]4)[C:18]=3[CH:36]=2)[CH2:9][CH2:8]1)([CH3:6])[CH3:5].[OH-].[Na+]>CO.O>[F:37][C:15]1[C:14]([S:13][CH:10]2[CH2:11][CH2:12][N:7]([C:4]([CH3:6])([CH3:5])[C:3]([OH:38])=[O:2])[CH2:8][CH2:9]2)=[CH:36][C:18]2[C:19]3[N:23]([CH2:24][CH2:25][O:26][C:17]=2[CH:16]=1)[CH:22]=[C:21]([C:27]1[N:28]([CH:33]([CH3:35])[CH3:34])[N:29]=[C:30]([CH3:32])[N:31]=1)[N:20]=3

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 683130922-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-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 683126382-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-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 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-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 (0.394 mmol) in MeOH (3 mL) was added 2.0M NaOH in water (1 mL). The reaction mixture was heated at 100° C. for 1 h using microwave irradiation. The crude mixture was purified by column chromatography (C18, gradient 20-60% MeOH in 0.003M HCl/H2O) then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 0.5M NH3/MeOH. The product containing fractions were combined and concentrated under reduced pressure affording 2-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-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 as a yellow solid (177 mg, 85% over two steps). LCMS: RT 2.32, 2.37, 2.44 min [M−H]− 526.8

Workup

  1. custommicrowave irradiation
  2. customThe crude mixture was purified by column chromatography (C18, gradient 20-60% MeOH in 0.003M HCl/H2O)
  3. washwas washed with MeOH
  4. washthe product eluted with 0.5M NH3/MeOH
  5. additionThe product containing fractions
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-83aee7f7b89742528a8ec74127cfcef2
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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