Diisopropylethylamine → N'-(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carbonyl)-N'-isopropyl-hydrazinecarboxylic acid tert-butyl ester

HRID 708285Notes

Reaction equation

HRID 708285 reaction equation
[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]=[C:8]([C:14]([OH:16])=O)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.[C:19]([O:23][C:24]([NH:26][NH:27][CH:28]([CH3:30])[CH3:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:19]([O:23][C:24]([NH:26][N:27]([C:14]([C:8]1[S:9][C:10]2[CH2:11][CH2:12][O:13][C:4]3[CH:3]=[C:2]([Br:1])[CH:18]=[CH:17][C:5]=3[C:6]=2[N:7]=1)=[O:16])[CH:28]([CH3:30])[CH3:29])=[O:25])([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11217534N'-(propan-2-yl)(tert-butoxy)carbohydrazideHCID 579001668-Bromo-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylic acid

Product 1

HCID 58204215N'-(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carbonyl)-N'-isopropyl-hydrazinecarboxylic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (5.20 g, 16.0 mmol) and N′-isopropyl-hydrazinecarboxylic acid tert-butyl ester (3.33 g, 19.1 mmol) in DMF (100 mL) at 0° C. was added DIPEA (6.93 mL, 39.9 mmol) followed by HATU (9.09 g, 23.9 mmol). The reaction mixture was stirred at RT for 72 h before being concentrated in vacuo. The resultant residue was treated with water then extracted with DCM (×3) before the combined organic extracts were washed with 10% citric acid, then saturated sodium bicarbonate solution followed by brine. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give a brown oil. The oil was extracted with diethyl ether (×5) and the diethyl ether extracts concentrated in vacuo before being triturated with pentane to give the title compound as a light brown solid (6.14 g, 12.7 mmol, 80%). LCMS: RT=5.02 min, [M+H]+=482/484.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. additionThe resultant residue was treated with water
  3. extractionthen extracted with DCM (×3) before the combined organic extracts
  4. washwere washed with 10% citric acid
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a brown oil
  9. extractionThe oil was extracted with diethyl ether (×5)
  10. concentrationthe diethyl ether extracts concentrated in vacuo
  11. custombefore being triturated with pentane

Sources & evidence

ORD record
ord-2e708a8264384bd49b2e5361b7888a92
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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