Cyclopropanecarbohydrazide → N'-(cyclopropanecarbonyl)-3-iodo-1-tosyl-1H-indole-5-carbohydrazide

HRID 634199Notes

Reaction equation

HRID 634199 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([OH:13])=O)[CH:9]=2)[N:4]([S:14]([C:17]2[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:3]=1.[CH:24]1([C:27]([NH:29][NH2:30])=[O:28])[CH2:26][CH2:25]1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.O>[CH:24]1([C:27]([NH:29][NH:30][C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([S:14]([C:17]2[CH:18]=[CH:19][C:20]([CH3:21])=[CH:22][CH:23]=2)(=[O:16])=[O:15])[CH:3]=[C:2]3[I:1])=[O:13])=[O:28])[CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 81396CyclopropanecarbohydrazideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 683285993-iodo-1-tosyl-1H-indole-5-carboxylic acid

Product 1

HCID 68328486N'-(cyclopropanecarbonyl)-3-iodo-1-tosyl-1H-indole-5-carbohydrazideYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring suspension of 3-iodo-1-tosyl-1H-indole-5-carboxylic acid (1.944 g, 4.41 mmol) and cyclopropanecarbohydrazide (0.441 g, 4.41 mmol) (Enamine) in THF (40 mL) was added N-ethyl-N-isopropylpropan-2-amine (1.919 mL, 11.01 mmol) (Sigma-Aldrich) followed by HATU (1.843 g, 4.85 mmol) (Oakwood Products) in one portion and the solution was stirred at RT for 45 min. Several ice chunks were added to the mixture followed by H2O (75 mL). The mixture was extracted with EtOAc (2×100 mL). The organic layer was washed with 50 mL of sat. NaHCO3, then brine, dried over MgSO4, filtered, and concentrated to a volume of about 50 mL of EtOAc. A precipitate formed and was isolated by filtration. The filter cake was washed with EtOAc (2×10 mL) to give N′-(cyclopropanecarbonyl)-3-iodo-1-tosyl-1H-indole-5-carbohydrazide (1.13 g, 2.159 mmol, 49.0%) as an off-white solid. MS (ESI, pos. ion) m/z: 523.8 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.49 (s, 1H), 10.14 (s, 1H), 8.14-8.21 (m, 1H), 8.01-8.09 (m, 1H), 7.89-8.01 (m, 4H), 7.41 (d, J=8.2 Hz, 2H), 2.32 (s, 3H), 1.63-1.74 (m, 1H), 0.63-0.87 (m, 4H).

Workup

  1. additionSeveral ice chunks were added to the mixture
  2. extractionThe mixture was extracted with EtOAc (2×100 mL)
  3. washThe organic layer was washed with 50 mL of sat. NaHCO3
  4. dry with materialbrine, dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to a volume of about 50 mL of EtOAc
  7. customA precipitate formed
  8. customwas isolated by filtration
  9. washThe filter cake was washed with EtOAc (2×10 mL)

Sources & evidence

ORD record
ord-0ff376b6eab4480b8a583b42364b8ca6
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

Loading…