1H-Indole-5-Carboxylic Acid → tert-butyl 4-(1H-indol-5-ylcarbonyl)piperazine-1-carboxylate

HRID 521745Notes

Reaction equation

HRID 521745 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([OH:12])=O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CCN(C(C)C)C(C)C.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:10]([C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[NH:1][CH:2]=[CH:3]3)=[O:12])[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 742801H-Indole-5-Carboxylic AcidHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 42535715tert-butyl 4-(1H-indol-5-ylcarbonyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1H-indole-5-carboxylic acid (323 mg, 2.0 mmol) in 10 mL of DCM was added DIPEA (1.03 g, 8.0 mmol) and piperazine-1-carboxylic acid tert-butyl ester (400 mg, 2.1 mmol). HBTU (1.14 g, 3.0 mmol) was added at 0° C. The resulting mixture was stirred at r.t. for 18 h. TLC indicated that the starting material was gone. The mixture was diluted with DCM (100 mL) and washed with water (30 mL). The organic layer was separated and dried over anhydrous Na2SO4. The solution was concentrated to give a crude product, which was then purified with silica gel column (Hexane/EtOAc=1/1) to give HJC-2-13 (605 mg, 92%) as a yellow oil. 1H NMR (600 MHz, CDCl3) δ 8.44 (s, 1H), 7.73 (s, 1H), 7.40 (d, 1H, J=8.4 Hz), 7.26-7.27 (m, 2H), 6.59 (s, 1H), 3.56-3.63 (m, 4H), 3.42-3.47 (m, 4H), 1.47 (s, 9H).

Workup

  1. washwashed with water (30 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-0b278f21607c4cf59807f52396b07215
Source dataset
uspto-grants-2016_05
Patent number
US09328125B2

Reaction notes

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