1,2-Dichloroethane → 4-[(4-Cyclobutylmethoxy-1H-indole-2-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1929196Notes

Reaction equation

HRID 1929196 reaction equation
Cl.Cl.OC1CCN(CCN2CCC(N[C:19]([C:21]3[NH:22][C:23]4[C:28]([CH:29]=3)=[C:27]([O:30][CH2:31][CH2:32][C:33]([CH3:36])(C)C)[CH:26]=[CH:25][CH:24]=4)=[O:20])CC2)CC1.[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][CH:47]([NH2:50])[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38].[CH:51]1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.C(Cl)CCl>C(Cl)Cl>[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][CH:47]([NH:50][C:19]([C:21]2[NH:22][C:23]3[C:28]([CH:29]=2)=[C:27]([O:30][CH2:31][CH:32]2[CH2:33][CH2:36][CH2:51]2)[CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:38])[CH3:39]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 12682914-Amino-1-Boc-piperidineHCID 668413154-(3,3-Dimethyl-butoxy)-1H-indole-2-carboxylic acid {1-[2-(4-hydroxy-piperidin-1-yl)-ethyl]-piperidin-4-yl}-amide dihydrochloride

Product 1

HCID 668413964-[(4-Cyclobutylmethoxy-1H-indole-2-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-cyclobutylmethoxy-1H-indole-2-carboxylic acid (82) from example 34 (2.2 g, 8.97 mmol) in 20 ml of DCM is added 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.98 g, 9.87 mmol), HOBT (1.37 g, 8.97 mmol), triethylamine (2.5 ml, 17.94 mmol) and EDC (1.72 g, 8.97 mmol). The mixture is stirred at room temperature over night. It is then washed with 2N-NaOH and brine, dried over anhydrous sodium sulphate and evaporated to give a yellow powder. The crude material is purified by chromatography on silicagel using hexane and EtOAc (from 0% to 20%).

Workup

  1. washIt is then washed with 2N-NaOH and brine
  2. dry with materialdried over anhydrous sodium sulphate
  3. customevaporated
  4. customto give a yellow powder
  5. customThe crude material is purified by chromatography on silicagel

Sources & evidence

ORD record
ord-0d23ad756161477e96f94868f888ebc7
Source dataset
uspto-grants-2012_05
Patent number
US08183366B2

Reaction notes

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