1-Hydroxybenzotriazole → tert-butyl 5-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 2241348Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2241348
[CH3:1][O:2][C:3]1[CH:42]=[CH:41][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([N:26]3[CH2:30][CH:29]4[CH2:31][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:33][CH:28]4[CH2:27]3)=[N:9]2)=[CH:5][CH:4]=1.[F:43][C:44]1[CH:49]=[CH:48][C:47]([N:50]2[C:55](=[O:56])[C:54]([C:57](O)=[O:58])=[CH:53][CH:52]=[N:51]2)=[CH:46][CH:45]=1.Cl.C(N=C=NCCCN(C)C)C.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[F:25][C:19]1[CH:20]=[C:21]([NH:24][C:57]([C:54]2[C:55](=[O:56])[N:50]([C:47]3[CH:48]=[CH:49][C:44]([F:43])=[CH:45][CH:46]=3)[N:51]=[CH:52][CH:53]=2)=[O:58])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:42][CH:41]=3)[N:9]=[C:10]([N:26]3[CH2:30][CH:29]4[CH2:31][N:32]([C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])[CH2:33][CH:28]4[CH2:27]3)[C:11]=12

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 68514742tert-butyl 5-(4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

Produkt 1

HCID 68512270tert-butyl 5-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylateAusbeute 68,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A round-bottomed flask was charged with tert-butyl 5-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (44.8 mg, 0.0780 mmol), 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (54.8 mg, 0.234 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (74.7 mg, 0.390 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (52.7 mg, 0.390 mmol), N-ethyl-N-isopropylpropan-2-amine (101 mg, 0.780 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature overnight. The reaction was partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (42.5 mg, 68.9%). LRMS (APCI pos): m/e 691 (M−99).

Aufarbeitung

  1. customThe reaction was partitioned between EtOAc and H2O
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1

Quellen und Nachweise

ORD-Eintrag
ord-7388f82a724b45f7bd1adb2696009546
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07723330B2

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