Trifluoroacetic acid → 6-tert-butyl 2-methyl 7,8-dihydropyrrolo[3,2-e]indole-2,6(3H)-dicarboxylate

HRID 1183813Notes

Reaction equation

HRID 1183813 reaction equation
[CH:1]1[C:5]2=[C:6]3[C:10]([CH:11]=[CH:12][C:4]2=[N:3][C:2]=1[C:13]([O:15][CH3:16])=[O:14])=[N:9][CH:8]=[CH:7]3.N1[CH2:22][CH2:21][CH2:20]CC1.C1C2=C3C(=CC=C2NC1)NC([C:35]([O:37]C)=[O:36])=C3.[C:39](O)(C(F)(F)F)=O>CN(C=O)C.CCN(C(C)C)C(C)C>[C:21]([O:37][C:35]([N:9]1[C:10]2[C:6](=[C:5]3[C:4](=[CH:12][CH:11]=2)[NH:3][C:2]([C:13]([O:15][CH3:16])=[O:14])=[CH:1]3)[CH2:7][CH2:8]1)=[O:36])([CH3:20])([CH3:22])[CH3:39]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8082PiperidineHCID 15480266Methyl 3,6,7,8-tetrahydropyrrolo[3,2-e]indole-2-carboxylateHCID 178496869HCID 178496869, compound

Product 1

HCID 151147736-tert-butyl 2-methyl 7,8-dihydropyrrolo[3,2-e]indole-2,6(3H)-dicarboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3 (15 mg, 0.014 mmol) in DMF (2 mL) was treated with 5% piperidine in DMF (2 mL) and the reaction mixture was stirred for 10 min at 25° C. The crude product was precipitated with diethyl ether and used for the next step without further purification. The crude product was dissolved in DMF (3 mL) followed by the addition of 4 (25 mg, 0.025 mmol) in DMF (2 mL) and DIEA (20 uL). The reaction mixture was stirred for 2 hrs at room temperature. TFA was added to the reaction mixture and the reaction mixture was stirred at room temperature for 45 min to yield compound 5 as indicated by analytical HPLC. Crude product was purified by Prep HPLC (SymmetrPrep C18, 7 μm, 19×150 mm column), eluted at 10 ml/min (0.01% TFA in water/acetonitrile) with a gradient: 10% acetonitrile in 5 min, 10% to 50% acetonitrile in 15 min, maintaining 50% acetonitrile in 5 min, 50% to 100% acetonitrile in 5 min, to obtain 5 (3 mg, 94%). MS: (MH)+ 889.

Workup

  1. customThe crude product was precipitated with diethyl ether
  2. customused for the next step without further purification
  3. dissolutionThe crude product was dissolved in DMF (3 mL)
  4. stirringThe reaction mixture was stirred for 2 hrs at room temperature
  5. stirringthe reaction mixture was stirred at room temperature for 45 min

Sources & evidence

ORD record
ord-440b70ca10bb44bf8a49318adf694142
Source dataset
uspto-grants-2014_03
Patent number
US08664407B2

Reaction notes

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