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

HRID 2227735Notes

Reaction equation

HRID 2227735 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 14%

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, 14%).

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

Sources & evidence

ORD record
ord-9c51847d947d4939b56e4726d2d6a20b
Source dataset
uspto-grants-2002_07
Patent number
US06414144B1

Reaction notes

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