Diisopropylethylamine → 3-Amino-5-[4-tert-butoxycarbonylamino-2-(3,4-dichloro-phenyl)-butyrylamino]-indazole-1-carboxylic acid tert-butyl ester

HRID 1823909Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1823909
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH2:17])=[CH:14][CH:15]=2)[C:10]([NH2:18])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:43]([O:47][C:48]([NH:50][CH2:51][CH2:52][CH:53]([C:57]1[CH:62]=[CH:61][C:60]([Cl:63])=[C:59]([Cl:64])[CH:58]=1)[C:54](O)=[O:55])=[O:49])([CH3:46])([CH3:45])[CH3:44].C(N(C(C)C)CC)(C)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:54](=[O:55])[CH:53]([C:57]3[CH:62]=[CH:61][C:60]([Cl:63])=[C:59]([Cl:64])[CH:58]=3)[CH2:52][CH2:51][NH:50][C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:49])=[CH:14][CH:15]=2)[C:10]([NH2:18])=[N:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 221479534-tert-Butoxycarbonylamino-2-(3,4-dichlorophenyl)-butyric acidHCID 23571038tert-butyl 3,5-diamino-1H-indazole-1-carboxylate

Produkt 1

HCID 235710413-Amino-5-[4-tert-butoxycarbonylamino-2-(3,4-dichloro-phenyl)-butyrylamino]-indazole-1-carboxylic acid tert-butyl esterAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirred solution of 3,5-diamino-indazole-1-carboxylic acid tert-butylester (2.17 g, 8.75 mmol), PyBroP (4.1 g, 8.75 mmol) and 4-tert-butoxycarbonylamino-2-(3,4-dichloro-phenyl)-butyric acid (3 g, 8.75 mmol) in dichloromethane (100 mL) was added diisopropylethylamine (3.0 mL, 17.5 mmol) at 0° C. The resulting mixture was allowed to warm to room temperature over 4 hours then was concentrated and the residue partitioned between EtOAc and ammonium chloride (saturated, aqueous). The organic phase was separated and washed with sodium bicarbonate (saturated, aqueous), then dried (sodium sulfate) and concentrated to a brown foam. Purification by column chromatography (silica, 20% petroleum ether-EtOAc gave the title compound as a light brown solid (2.92 g, 58%); 1H NMR (400 MHz, DMSO) 1.36 (9H, s), 1.56 (9H, s), 1.80–1.90 (1H, m), 2.10–2.20 (1H, m), 2.89 (2H, m), 6.29 (2H, brs), 6.87 (1H, t), 7.38 (1H, d), 7.45 (1H, d), 7.61–7.65 (2H, m), 7.90 (1H, m), 8.19 (1H, s), 10.30 (1H, s); MS (ES+) m/e=578.

Aufarbeitung

  1. concentrationthen was concentrated
  2. customthe residue partitioned between EtOAc and ammonium chloride (saturated, aqueous)
  3. customThe organic phase was separated
  4. washwashed with sodium bicarbonate (saturated, aqueous)
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated to a brown foam
  7. customPurification by column chromatography (silica, 20% petroleum ether-EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-7da8f2633a434db3a7fcc1cfc1a04d1b
Quelldatensatz
uspto-grants-2006_05
Patentnummer
US07041687B2

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