6-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one → 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one

HRID 925625Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 925625
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[N:15]([CH3:16])[CH2:14][CH2:13][CH2:12][C:11]=13)[N:8]=[CH:7][N:6]([C@H:17]1[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]1[OH:23])[C:5]2=[O:24].[Cl-].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][Zn+])=[CH:29][N:28]=1>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:26][C:27]1[N:28]=[CH:29][C:30]([CH2:33][C:2]2[CH:3]=[C:4]3[C:9](=[C:10]4[N:15]([CH3:16])[CH2:14][CH2:13][CH2:12][C:11]=24)[N:8]=[CH:7][N:6]([C@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]2[OH:23])[C:5]3=[O:24])=[CH:31][CH:32]=1

Komponenten

5

Edukt 2

HCID 710421236-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-oneHCID 178478124HCID 178478124, Verbindung

Produkt 1

HCID 714717346-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 6-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one (40 mg, 0.10 mmol) in THF (0.4 mL) at 0° C. was added (2-chloro-5-pyridyl)methylzinc chloride (0.5 M in THF, 408 μL, 0.20 mmol) and Pd(PtBu3)2. The mixture was warmed to rt and stirred for 30 min. The resulting solution was quenched with water and extracted with CH2Cl2. The combined extracts were dried (Na2SO4) and concentrated. Purification by silica gel chromatography (0-5% MeOH/CH2Cl2) afforded 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one in pure form: 1H NMR (400 MHz, CD3OD); 1H NMR (400 MHz, CDCl3) 8.20 (d, J=2.3 Hz, 1H), 8.03 (s, 1H), 7.59 (s, 1H), 7.33 (dd, J=2.3, 8.2 Hz, 1H), 7.17 (d, J=8.2 Hz, 1H), 4.51 (m, 1H), 3.96 (s, 2H), 3.90 (m, 1H), 3.12 (t, J=5.2 Hz, 2H), 3.08 (s, 3H), 2.56 (t, J=6.5 Hz, 2H), 2.24-2.15 (m, 2H), 2.00-1.92 (m, 2H), 1.89-1.75 (m, 4H), 1.55-1.37 (m, 2H); HRMS (MH+) calcd for C24H28ClN4O2 439.1895. found 439.1894.

Aufarbeitung

  1. customThe resulting solution was quenched with water
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (0-5% MeOH/CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-6d8db76fead54a209f70badc2adbf36c
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284312B2

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