Sodium Hydroxide → 4-Isobutoxy-1H-indole-2-carboxylic acid [1-(2-hydroxy-ethyl)-piperidin-4-yl]-amide

HRID 2267927Notes

Reaction equation

HRID 2267927 reaction equation
N1([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][CH:13]([NH:16][C:17]([C:19]3[NH:20][C:21]4[C:26]([CH:27]=3)=[C:25]([O:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH:24]=[CH:23][CH:22]=4)=[O:18])[CH2:12][CH2:11]2)CCCCCC1.CCN(C(C)C)C(C)C.NC1CCN(CC[OH:51])CC1.[OH-].[Na+].C1CN([P+](ON2N=NC3C2=CC=CC=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C.CCOCC>[OH:51][CH2:8][CH2:9][N:10]1[CH2:11][CH2:12][CH:13]([NH:16][C:17]([C:19]2[NH:20][C:21]3[C:26]([CH:27]=2)=[C:25]([O:28][CH2:29][CH:30]([CH3:31])[CH3:32])[CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:14][CH2:15]1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 114420474-Isobutoxy-1H-indole-2-carboxylic acid [1-(2-azepan-1-yl-ethyl)-piperidin-4-yl]-amideHCID 157334452-(4-Aminopiperidin-1-yl)ethan-1-ol

Product 1

HCID 668416274-Isobutoxy-1H-indole-2-carboxylic acid [1-(2-hydroxy-ethyl)-piperidin-4-yl]-amide

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4-Isobutoxy-1H-indole-2-carboxylic acid 80 (preparation see Example 8, 1 g, 4.29 mmol) is suspended in 5 ml of DMF, cooled to 0° C. and treated with Hünig's Base (1.46 ml, 8.58 mmol). The mixture is stirred for 15 min at 0° C. In a separate reaction flask, compound 192 (931 mg, 4.29 mmol) in 10 ml of DMF is cooled to 0° C., treated with 10M aqueous sodium hydroxide solution (0.858 ml, 8.58 mmol) and stirred for 15 min at this temperature. This solution is added to the above mentioned mixture, followed by benzotriazol-1-yl-oxytripyrrolidinphosphonium hexafluorophosphate (PyBOP, 2.34 g, 4.5 mmol) and stirred for 4 h at room temperature. The reaction mixture is diluted with ethyl acetate and washed with 2N sodium hydroxide solution, water and brine. Evaporation gave a semisolid, yellow crude product, which is treated with ether, filtered of and washed with ether.

Workup

  1. temperatureis cooled to 0° C.
  2. stirringstirred for 15 min at this temperature
  3. additionThis solution is added to the
  4. stirringstirred for 4 h at room temperature
  5. washwashed with 2N sodium hydroxide solution, water and brine
  6. customEvaporation
  7. customgave a semisolid, yellow crude product, which
  8. filtrationfiltered of and
  9. washwashed with ether

Sources & evidence

ORD record
ord-05ba8017ba674b1a8e1ee3b932e86a8b
Source dataset
uspto-grants-2010_12
Patent number
US07858781B2

Reaction notes

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