1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 4-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate

HRID 2241331Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2241331
[NH2:1][C:2]1[CH:39]=[CH:38][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[N:13]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[N:14]=[C:15]([N:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[C:8]=23)=[C:4]([F:40])[CH:3]=1.[F:41][C:42]1[CH:47]=[CH:46][C:45]([N:48]2[CH2:53][CH:52]3[C:50]([C:54](O)=[O:55])([CH2:51]3)[C:49]2=[O:57])=[CH:44][CH:43]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH4+].[Cl-]>CN(C=O)C>[CH3:37][O:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][N:13]2[C:9]3=[N:10][CH:11]=[CH:12][C:7]([O:6][C:5]4[CH:38]=[CH:39][C:2]([NH:1][C:54]([C:50]56[CH2:51][CH:52]5[CH2:53][N:48]([C:45]5[CH:46]=[CH:47][C:42]([F:41])=[CH:43][CH:44]=5)[C:49]6=[O:57])=[O:55])=[CH:3][C:4]=4[F:40])=[C:8]3[C:15]([N:16]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:20][CH2:21]3)=[N:14]2)=[CH:31][CH:32]=1

Komponenten

7

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 673496483-(4-Fluorophenyl)-2-oxo-3-azabicyclo[3.1.0]hexane-1-carboxylic acidHCID 68510616tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate

Produkt 1

HCID 68514115tert-butyl 4-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylateAusbeute 71,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperazine-1-carboxylate (100 mg, 0.182 mmol, obtained from Example 82 Step A), 3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxylic acid (85.7 mg, 0.365 mmol, obtained from Example 98 Step D), EDCI (210 mg, 1.09 mmol) and HOBT (148 mg, 1.09 mmol) was stirred in DMF (6 mL) for 12 hours. The reaction mixture was poured into saturated aqueous NH4Cl and extracted with EtOAc. The organic layer was washed with saturated aqueous NaHCO3, 10% aqueous LiCl, dry with Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (5% MeOH in CH2Cl2) to afford the product (100 mg, 71.6% yield) as a white solid. LRMS (APCI pos) m/e 766.2 (M+1).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with saturated aqueous NaHCO3, 10% aqueous LiCl
  3. dry with materialdry with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash silica gel chromatography (5% MeOH in CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-0b7473360be2491db34e861667b3208b
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07723330B2

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