Diisopropylethylamine → 4-{[4-(5-fluoro-benzofuran-3-ylmethoxy)-1H-indole-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1929203Notes

Reaction equation

HRID 1929203 reaction equation
[C@H]1([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19]([C:21]3[NH:22][C:23]4[C:28]([CH:29]=3)=[C:27]([O:30][CH2:31][C:32]3[C:36]5[CH:37]=[C:38]([F:41])[CH:39]=[CH:40][C:35]=5[O:34][CH:33]=3)[CH:26]=[CH:25][CH:24]=4)=[O:20])[CH2:14][CH2:13]2)[C@@H]2N(CCCC2)CCC1.CCN(C(C)C)C(C)C.[C:51]([O:55]C(=O)NC1CCNCC1)([CH3:54])([CH3:53])[CH3:52].C1CN([P+]([O:81]N2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[C:51]([O:55][C:11]([N:12]1[CH2:13][CH2:14][CH:15]([NH:18][C:19]([C:21]2[NH:22][C:23]3[C:28]([CH:29]=2)=[C:27]([O:30][CH2:31][C:32]2[C:36]4[CH:37]=[C:38]([F:41])[CH:39]=[CH:40][C:35]=4[O:34][CH:33]=2)[CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:16][CH2:17]1)=[O:81])([CH3:54])([CH3:53])[CH3:52]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 2724699PyBOPHCID 596001954-(5-Fluoro-benzofuran-3-ylmethoxy)-1H-indole-2-carboxylic acid {1-[(1S,9aR)-1-(octahydro-quinolizin-1-yl)methyl]-piperidin-4-yl}-amide

Product 1

HCID 668414554-{[4-(5-fluoro-benzofuran-3-ylmethoxy)-1H-indole-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(5-fluoro-benzofuran-3-ylmethoxy)-1H-indole-2-carboxylic acid (113, see example 60, 160 mg, 0.49 mmol) is dissolved in 1.5 ml of DMF and cooled to 0° C. After addition of Huenigs base (252 ul, 1.5 mmol) the mixture is stirred for 15 min, then piperidin-4-yl-carbamic acid tert-butyl ester (3, 98.5 mg, 0.49 mmol) is added, followed by PyBOP (269 mg, 0.51 mmol). The mixture is stirred at room temperature for 18 h. Then the mixture is diluted with ethyl acetate, washed 1N sodium hydroxide solution and brine. The organic layers are dried over sodium sulfate and evaporated under reduced pressure. The crude product (581 mg) is purified by flash-chromatography (silica gel, cyclohexane/ethyl acetate

Workup

  1. stirringThe mixture is stirred at room temperature for 18 h
  2. washwashed 1N sodium hydroxide solution and brine
  3. dry with materialThe organic layers are dried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe crude product (581 mg) is purified by flash-chromatography (silica gel, cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-c2486e8de9314a0c98c60c1a08a3b4c2
Source dataset
uspto-grants-2012_05
Patent number
US08183366B2

Reaction notes

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