1-Hydroxybenzotriazole → ethyl (2S)-2-[(1,2,3,4-tetrahydrocyclopenta[b]indol-5-ylcarbonyl)amino]propanoate

HRID 916610Notes

Reaction equation

HRID 916610 reaction equation
[CH2:1]1[C:12]2[C:11]3[C:6](=[C:7]([C:13]([OH:15])=O)[CH:8]=[CH:9][CH:10]=3)[NH:5][C:4]=2[CH2:3][CH2:2]1.[CH2:16]([O:18][C:19](=[O:23])[C@H:20]([CH3:22])[NH2:21])[CH3:17].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH2:1]1[C:12]2[C:11]3[CH:10]=[CH:9][CH:8]=[C:7]([C:13]([NH:21][C@@H:20]([CH3:22])[C:19]([O:18][CH2:16][CH3:17])=[O:23])=[O:15])[C:6]=3[NH:5][C:4]=2[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 76507L-Alanine ethyl esterHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 121329741H,2H,3H,4H-cyclopenta(b)indole-5-carboxylic acid

Product 1

HCID 12132975ethyl (2S)-2-[(1,2,3,4-tetrahydrocyclopenta[b]indol-5-ylcarbonyl)amino]propanoateYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred, cooled (0° C.) solution of crude 1,2,3,4-tetrahydrocyclopenta[b]indole-5-carboxylic acid (60 mmol, 12 g), L-alanine ethyl ester (72 mmol, 11 g), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC) (72 mmol, 14 g), 1-hydroxybenzotriazole (HOBT) (72 mmol, 10 g) in CH2Cl2 (100 mL) was slowly added diisopropylethylamine (360 mmol, 46 g). The reaction mixture was stirred overnight while warming to room temperature. The reaction was concentrated in vacuo and the resulting oil was partitioned between water and ethyl acetate. The organic layer was washed with saturated aqueous NH4Cl, NaHCO3, and brine, dried over MgSO4, filtered and concentrated to a brown oil. The crude material was purified by chromatography through silica gel (Biotage) eluting with 15% ethyl acetate-hexanes to afford a yellow oil (8.4 mmol, 2.5 g, 16% yield over 2 steps).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe resulting oil was partitioned between water and ethyl acetate
  3. washThe organic layer was washed with saturated aqueous NH4Cl, NaHCO3, and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to a brown oil
  7. customThe crude material was purified by chromatography through silica gel (Biotage)
  8. washeluting with 15% ethyl acetate-hexanes
  9. customto afford a yellow oil (8.4 mmol, 2.5 g, 16% yield over 2 steps)

Sources & evidence

ORD record
ord-8c456c8c307b472d94e774e42efa7310
Source dataset
uspto-grants-2007_09
Patent number
US07271163B2

Reaction notes

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