Benzylamine → 2-(3-formyl-1H-indol-1-yl)acetic acid

HRID 1162796Notes

Reaction equation

HRID 1162796 reaction equation
C(N=[C:5]=[N:6][CH:7]([CH3:9])[CH3:8])(C)C.C(N(CC)[CH:14]([CH3:16])[CH3:15])(C)C.ON1[C:24]2C=CC=[CH:28][C:23]=2N=N1.C(N)C1C=CC=CC=1.C([BH3-])#N.[Na+].[C:41]([O:44]C(=O)C)(=[O:43])C.C(N(CC)CC)C.C(O)(C(F)(F)F)=[O:56].C(Cl)Cl>CN(C=O)C.C(Cl)Cl.C([O-])(=O)C>[CH:28]([C:23]1[C:8]2[C:7](=[CH:9][CH:16]=[CH:14][CH:15]=2)[N:6]([CH2:5][C:41]([OH:44])=[O:43])[CH:24]=1)=[O:56]

Participants

10

Reactant 7

HCID 7504BenzylamineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 21863450Trifluoroacetic acid methylene chlorideHCID 21881581Acetic anhydride triethylamine

Product 1

HCID 7714652-(3-formyl-1H-indol-1-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 175AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

3-Formylindol-1-ylacetic acid was prepared and coupled to the beads above according to the process of EP 0 801 083 A2 (Estep et al.) using diisopropyl carbodiimide, N,N-diisopropylethylamine, and N-hydroxybenzotriazole in DMF/CH2Cl2. Benzylamine was reductively coupled to this bead-linker using sodium cyanoborohydride in 0.5M acetate buffer, pH 5, by the procedure in the same document. The product was then acetylated using acetic anhydride/triethylamine. The acetylated amine was released from the resin by treatment with 50% TFA/CH2Cl2 for 4 hours. The filtrate was evaporated to dryness and the residue evaluated by NMR and mass spectroscopy to show that the major product was N-benzylacetamide. This example demonstrates the feasibility of conducting solid phase synthesis using azlactone-functionalized beads.

Workup

  1. customThe filtrate was evaporated to dryness
  2. customsolid phase synthesis

Sources & evidence

ORD record
ord-45d2d54a1e6843298127398bdf4de6a0
Source dataset
uspto-grants-2010_10
Patent number
US07820785B2

Reaction notes

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