1H-Indole-3-propanoic acid → HCID 71468596, compound

HRID 1401082Notes

Reaction equation

HRID 1401082 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.C([O-])([O-])=O.[K+].[K+].N1C2C(=CC=CC=2)C(CCC(N(C(C)C)NC(=O)C2C=CC=CC=2)=O)=C1.[CH3:93][C:94]([O:97][C:98](OC(OC(C)(C)C)=O)=[O:99])([CH3:96])[CH3:95]>CN(C=O)C.CCOC(C)=O.C1COCC1.O>[C:20]([NH:19][N:18]([C:12](=[O:14])[CH2:11][CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]([C:98]([O:97][C:94]([CH3:96])([CH3:95])[CH3:93])=[O:99])[CH:2]=1)[CH:15]([CH3:17])[CH3:16])(=[O:27])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

11

Reactant 7

HCID 37441H-Indole-3-propanoic acidHCID 11430Potassium CarbonateHCID 188691-Benzoyl-2-isopropylhydrazineHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 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 71468596HCID 71468596, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

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. After adding K2CO3 to N′-(3-(1H-indol-3-yl)propanoyl)-N′-isopropylbenzohydrazide, nitrogen substitution, and dissolving in THF/H2O, (Boc)2O was slowly drop-wise added and refluxed for 12 hr. After the reaction mixture was concentrated under reduced pressure, the residue was separated through silica gel chromatography (n-hexane:EtOAc:methanol=15:3:1) and dried so that white solid form of tert-butyl 3-(3-(2-benzoyl-1-isopropylhydrazinyl)-3-oxopropyl)-1H-indole-1-carboxylate was obtained. (285.9 mg, 60%)

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
  8. temperaturerefluxed for 12 hr
  9. concentrationAfter the reaction mixture was concentrated under reduced pressure
  10. customthe residue was separated through silica gel chromatography (n-hexane:EtOAc:methanol=15:3:1)
  11. dry with materialdried so that white solid form of tert-butyl 3-(3-(2-benzoyl-1-isopropylhydrazinyl)-3-oxopropyl)-1H-indole-1-carboxylate
  12. customwas obtained

Sources & evidence

ORD record
ord-fa915e57595d4cb48b404be9a5e1b607
Source dataset
uspto-grants-2014_12
Patent number
US08906952B2

Reaction notes

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