Diisopropylethylamine → 4-[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1786472Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1786472
Cl.[Cl:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]([OH:14])=O)[NH:9]2)=[CH:5][C:4]=1[O:15][CH:16]1[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]1.[Cl-].[Li+].[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:12]([C:8]2[NH:9][C:10]3[C:6]([CH:7]=2)=[CH:5][C:4]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]2)=[C:3]([Cl:2])[CH:11]=3)=[O:14])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:28])[CH3:29]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 433294Lithium ChlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 670179056-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1h-indole-2-carboxylic acid hydrochloride salt

Produkt 1

HCID 685649604-[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride salt with 1 eq. lithium chloride (760 mg, 1.0 eq.), tert-butyl-1-piperazinecarboxylate (467 mg, 1.25 eq.), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (838 mg, 1.25 eq.) and N,N-diisopropylethylamine (2.43 mL, 7 eq.) in N,N-dimethylformamide (9 mL) was stirred at room temperature for 20 h. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous sodium hydrogencarbonate solution. The organic layer was separated and washed with water and brine, and dried over sodium sulfate, filtered and the solvents were removed in vacuo. The residue was purified by flash chromatography on silica gel with a 19:1:0 to 90:9:1 gradient of dichloromethane/methanol/ammonia as eluant, to afford 577 mg (57%) of the title compound as a light-yellow solid.

Aufarbeitung

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvents were removed in vacuo
  7. customThe residue was purified by flash chromatography on silica gel with a 19:1:0 to 90:9:1 gradient of dichloromethane/methanol/ammonia as eluant

Quellen und Nachweise

ORD-Eintrag
ord-738d11a3f8a34cebbe5ca2ff2b99cedf
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07507736B2

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