1H-Indole-3-propanoic acid → HCID 71468593, compound

HRID 1401079Notes

Reaction equation

HRID 1401079 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][C:12]([OH:14])=O)=[CH:2]1.[CH:15]([NH:18][NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH3:17])[CH3:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[H-].[Na+].N1[C:71]2[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=2)[C:65](CCC(N(C(C)C)NC(=O)C2C=CC=CC=2)=O)=C1.BrCC1C=CC=CC=1>CN(C=O)C.CCOC(C)=O>[CH2:65]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][C:12]([N:18]([CH:15]([CH3:17])[CH3:16])[NH:19][C:20](=[O:27])[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:14])=[CH:2]1)[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1

Participants

10

Reactant 7

HCID 37441H-Indole-3-propanoic acidHCID 7498Benzyl BromideHCID 188691-Benzoyl-2-isopropylhydrazineHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71468595HCID 71468595, compound

Product 1

HCID 71468593HCID 71468593, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent2×

Procedure

To solution containing 3-(1H-indol-3-yl)propanoic acid (200 mg, 1.06 mmol), N′-isopropylbenzohydrazide (283.4 mg, 1.59 mmol) and HATU (604.6 mg, 1.59 mmol) dissolved in DMF (7.0 ml), N,N-diisopropylethylamine (DIPEA)(0.277 ml, 1.59 mmol) was slowly drop-wise added and stirred at room temperature for 12 hr. The reaction mixture was diluted with EtOAc, washed with water and brine, dried with anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was separated through silica gel chromatography (n-hexane:EtOAc:methanol=20:3:1) and dried so that white solid form of N′-(3-(1H-indol-3-yl)propanoyl)-N′-isopropylbenzohydrazide was obtained (350 mg, 95%). In 2-neck round bottom flask, NaH (5.5 mg, 0.23 mmol) dissolved in DMF at 0° C. was stirred, and solution containing N′-(3-(1H-indol-3-yl)propanoyl)-N′-isopropylbenzohydrazide (20 mg, 0.06 mmol) dissolved in DMF was transported and stirred at 0° C. for 30. The reaction mixture was drop-wise added with (bromomethyl)benzene (0.01634 ml, 0.14 mmol), and stirred at 80° C. for 1 hr. The reaction mixture was diluted with EtOAc, washed with water and brine, dried with anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was separated through silica gel chromatography (n-hexane:EtOAc=2:1) and dried so that ivory solid form of N′-(3-(1-benzyl-1H-indol-3-yl)propanoyl)-N′-isopropylbenzohydrazide was obtained (5 mg, 20%).

Workup

  1. washwashed with water and brine
  2. dry with materialdried with anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was separated through silica gel chromatography (n-hexane:EtOAc:methanol=20:3:1)
  6. dry with materialdried so that white solid form of N′-(3-(1H-indol-3-yl)propanoyl)-N′-isopropylbenzohydrazide
  7. customwas obtained (350 mg, 95%)
  8. stirringwas stirred
  9. stirringstirred at 0° C. for 30
  10. stirringstirred at 80° C. for 1 hr
  11. washwashed with water and brine
  12. dry with materialdried with anhydrous MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was separated through silica gel chromatography (n-hexane:EtOAc=2:1)
  16. dry with materialdried so that ivory solid form of N′-(3-(1-benzyl-1H-indol-3-yl)propanoyl)-N′-isopropylbenzohydrazide
  17. customwas obtained (5 mg, 20%)

Sources & evidence

ORD record
ord-33f95c531c514798998f82050131d6e6
Source dataset
uspto-grants-2014_12
Patent number
US08906952B2

Reaction notes

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