Diisopropylethylamine → 4-{[4-(Benzofuran-3-ylmethoxy)-1H-indole-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1929202Notes

Reaction equation

HRID 1929202 reaction equation
Cl.Cl.[C@H]1(CN2CCC(N[C:21]([C:23]3[NH:24][C:25]4[C:30]([CH:31]=3)=[C:29]([O:32][CH2:33][C:34]3[C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=5[O:36][CH:35]=3)[CH:28]=[CH:27][CH:26]=4)=[O:22])CC2)[C@@H]2N(CCCC2)CCC1.CCN(C(C)C)C(C)C.[C:52]([O:56][C:57]([N:59]1[CH2:64][CH2:63][CH:62]([NH2:65])[CH2:61][CH2:60]1)=[O:58])([CH3:55])([CH3:54])[CH3:53].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(OCC)(=O)C>[C:52]([O:56][C:57]([N:59]1[CH2:64][CH2:63][CH:62]([NH:65][C:21]([C:23]2[NH:24][C:25]3[C:30]([CH:31]=2)=[C:29]([O:32][CH2:33][C:34]2[C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[O:36][CH:35]=2)[CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:61][CH2:60]1)=[O:58])([CH3:55])([CH3:53])[CH3:54]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 2724699PyBOPHCID 668414964-(Benzofuran-3-ylmethoxy)-1H-indole-2-carboxylic acid {1-[(1S,9aR)-1-(octahydro-quinolizin-1-yl)methyl]-piperidin-4-yl}-amide dihydrochloride

Product 1

HCID 668416224-{[4-(Benzofuran-3-ylmethoxy)-1H-indole-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl esterYield 307.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a ice-cold solution of 4-(benzofuran-3-ylmethoxy)-1H-indole-2-carboxylic acid (105, see example 50) (200 mg, 0.651 mmol) in 2 ml of dimethylformamide is added Huenigs base (334 ul, 1.95 mmol). After stirring at 0° C. for 10 min, 4-amino-piperidine-1-carboxylic acid tert-butyl ester (130 mg, 0.651 mmol) and PyBOP (356 mg, 0.684 mmol) are added subsequently. The mixture is stirred at room temperature over night. It is then diluted with ethyl acetate, washed with 1N-NaOH and brine, dried over anhydrous sodium sulphate and evaporated to give 980 mg of a lightbrown oil. The crude material is purified by chromatography on silicagel using cyclohexane and ethylacetate (1:1).

Workup

  1. stirringThe mixture is stirred at room temperature over night
  2. washwashed with 1N-NaOH and brine
  3. dry with materialdried over anhydrous sodium sulphate
  4. customevaporated

Sources & evidence

ORD record
ord-449ff624e3814f8588c7be96a6763a85
Source dataset
uspto-grants-2012_05
Patent number
US08183366B2

Reaction notes

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