Water → 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide

HRID 575118Notes

Reaction equation

HRID 575118 reaction equation
[OH:1][C:2]([CH3:24])([CH3:23])[C:3]#[C:4][C:5]1[CH:6]=[CH:7][C:8]2[O:17][CH2:16][C:15](=[O:18])[C:14]3[S:13][C:12]([C:19]([NH2:21])=[O:20])=[N:11][C:10]=3[C:9]=2[CH:22]=1.[BH4-].[Na+].O>CO>[OH:18][CH:15]1[C:14]2[S:13][C:12]([C:19]([NH2:21])=[O:20])=[N:11][C:10]=2[C:9]2[CH:22]=[C:5]([C:4]#[C:3][C:2]([OH:1])([CH3:23])[CH3:24])[CH:6]=[CH:7][C:8]=2[O:17][CH2:16]1

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 717147149-(3-Hydroxy-3-methyl-but-1-ynyl)-4-oxo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide

Product 1

HCID 717147174-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amideYield 36.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 9-(3-Hydroxy-3-methyl-but-1-ynyl)-4-oxo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide (80 mg, 0.23 mmol) in MeOH (5 mL) at 0° C., NaBH4 (9 mg, 0.23 mmol) was added. The mixture was allowed to warm to room temperature, and stirred for 2 h, then water (2 mL) was added. The mixture was extracted with EtOAc (10 mL×3) and the combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%) to give 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as a white solid (29 mg, 36%). 1H NMR (400 MHz, DMSO-d6): 8.57 (d, J=2.1 Hz, 1H), 8.48 (s, 1H), 7.91 (s, 1H), 7.31 (dd, J1=8.3 Hz, J2=2.2 Hz, 1H), 7.07 (d, J=8.4 Hz, 1H), 6.38 (d, J=7.2 Hz, 1H), 5.45 (s, 1H), 5.09-5.14 (m, 1H), 4.08-4.35 (m, 2H), 1.49 (s, 6H); LC-MS (ESI & APCI): 345.3 (M+1).

Workup

  1. extractionThe mixture was extracted with EtOAc (10 mL×3)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%)

Sources & evidence

ORD record
ord-343eb2adc52f4f768c4b4ab1edb85f8e
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…