Potassium Carbonate → 2-[3-(hydroxymethyl)-4-[7-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-3H-benzimidazol-5-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one

HRID 1024084Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1024084
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:27][O:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1.C([O:31][CH2:32][C:33]1[C:34]([N:48]2[CH2:60][CH2:59][N:51]3[C:52]4[CH2:53][CH2:54][CH2:55][CH2:56][C:57]=4[CH:58]=[C:50]3[C:49]2=[O:61])=[N:35][CH:36]=[CH:37][C:38]=1B1OC(C)(C)C(C)(C)O1)(=O)C.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O1CCOCC1.O>[OH:31][CH2:32][C:33]1[C:34]([N:48]2[CH2:60][CH2:59][N:51]3[C:52]4[CH2:53][CH2:54][CH2:55][CH2:56][C:57]=4[CH:58]=[C:50]3[C:49]2=[O:61])=[N:35][CH:36]=[CH:37][C:38]=1[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:25][O:26][CH2:27]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 86684143(2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetateHCID 866841506-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-1H-benzo[d]imidazol-4-amine

Produkt 1

HCID 715573052-[3-(hydroxymethyl)-4-[7-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-3H-benzimidazol-5-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-oneAusbeute 15 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A microwave vial equipped with a magnetic stirrer was charged with 118b (200 mg, 0.52 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 114e (545 mg, 0.78 mmol), potassium carbonate (216 mg, 1.56 mmol), tris(dibenzylideneacetone) dipalladium(0) (48 mg, 0.052 mmol), tricyclohexylphosphine (146 mg, 0.52 mmol), water (0.2 mL), and dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, the sealed vial was irradiated under microwave at 110° C. for 1 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 118 as a white solid (50 mg, 15%). MS-ESI: [M+H]+ 646.3. 1H NMR (500 MHz, DMSO) δ 8.69 (d, J=2.0 Hz, 1H), 8.49 (d, J=5.0 Hz, 1H), 8.32-8.28 (m, 2H), 8.13 (s, 1H), 7.85-7.83 (m, 1H), 7.39-7.33 (m, 2H), 7.36 (s, 1H), 7.29 (s, 1H), 6.59 (s, 1H), 5.89 (s, 1H), 4.56 (t, J=6.5 Hz, 2H), 4.46 (t, J=6.5 Hz, 2H), 4.23-4.16 (m, 2H), 4.15-4.12 (m, 4H), 3.89-3.53 (m, 1H), 3.13-3.07 (m, 5H), 2.64-2.54 (m, 2H), 2.51-2.43 (m, 5H), 1.79-1.70 (m, 4H)

Aufarbeitung

  1. customA microwave vial equipped with a magnetic stirrer
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customthe sealed vial was irradiated under microwave at 110° C. for 1 h
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-7e98e48907ea4b999f58b695c120e79c
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722676B2

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