Dimethylformamide → 9-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (2-hydroxy-ethyl)-isopropyl-amide

HRID 707799Notes

Reaction equation

HRID 707799 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]([OH:17])=O)=[N:8][C:7]=3[C:6]=2[CH:18]=1.CN(C)C=O.C(N(CC)C(C)C)(C)C.[CH:33]([NH:36][CH2:37][CH2:38][OH:39])([CH3:35])[CH3:34]>>[OH:39][CH2:38][CH2:37][N:36]([CH:33]([CH3:35])[CH3:34])[C:15]([C:9]1[S:10][C:11]2[CH2:12][CH2:13][O:14][C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:18][C:6]=3[C:7]=2[N:8]=1)=[O:17]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 79942-(Isopropylamino)ethanolHCID 81531DiisopropylethylamineHCID 582039379-Bromo-4,5-dihydrobenzo[2,3]oxepino[4,5-D]thiazole-2-carboxylic acid

Product 1

HCID 582040029-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (2-hydroxy-ethyl)-isopropyl-amideYield 68%

Procedure

9-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (2.4 g, 7.4 mmol) was dissolved in N,N-Dimethylformamide (DMF, 50 mL, 600 mmol). Added N,N,N′N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uranium Hexafluorophosphate (3.1 g, 8.1 mmol) and N,N-Diisopropylethylamine (6.4 mL, 37 mmol) and let stir for 10 minutes. Added 2-(isopropylamino)ethanol (1.5 g, 15 mmol) and let the reaction stir for 2 hours. More N,N,N′N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uranium Hexafluorophosphate was added to the reaction (2.8 g, 7.4 mmol) and let the reaction stir for another 3 hours. Reaction was complete by LCMS. Concentrated in vacuo and flash purified on the ISCO 0 to 50% ethyl acetate in hexanes two times to give 9-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (2-hydroxy-ethyl)-isopropyl-amide (2.05 g, 68% yield).

Workup

  1. stirringstir for another 3 hours
  2. customReaction
  3. concentrationConcentrated in vacuo and flash
  4. custompurified on the ISCO 0 to 50% ethyl acetate in hexanes two times

Sources & evidence

ORD record
ord-ffdabdd300384136961670009aa569f3
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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