Cesium carbonate → 4-(1-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)morpholine

HRID 1923243

Reaktionsgleichung

Reaktionsgleichung von HRID 1923243
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:16][CH:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.[CH:29]([C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)([CH3:31])[CH3:30].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:29]([C:32]1[N:33]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][N:13]4[CH2:14][CH:15]([N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)[CH2:16]4)[N:8]3[CH3:11])=[C:4]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[N:3]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)([CH3:31])[CH3:30]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 221212-(propan-2-yl)-1H-1,3-benzodiazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596058532-Chloro-9-methyl-6-morpholin-4-yl-8-(3-morpholin-4-ylazetidin-1-ylmethyl)-9H-purine

Produkt 1

HCID 596060574-(1-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)morpholineAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
145 °C

Versuchsvorschrift

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-(3-morpholin-4-yl-azetidin-1-ylmethyl)-9H-purine (83 mg, 0.20 mmol), 2-isopropylbenzimidazole (39 mg, 0.24 mmol), tris(dibenzylideneacetone)dipalladium (9 mg, 0.01 mmol), Xphos (19 mg, 0.04 mmol) and Cs2CO3 (133 mg, 0.41 mmol) in dioxane (2 mL) was purged with argon then heated at 145° C. for 30 min in a microwave reactor. The reaction mixture was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified by column chromatography (Si—PCC, MeOH:DCM, 0-15%) affording 547 as a beige foam (72 mg, 68%). LCMS (Method I): RT 2.50 min, [M+H]+ 532.3. 1H NMR (CDCl3, 400 MHz): δ 7.89-7.84 (m, 1 H); 7.80-7.75 (m, 1 H); 7.29-7.21 (m, 2 H); 4.34 (m, 4 H); 4.00-3.92 (m, 3 H); 3.88-3.81 (m, 7 H); 3.76 (m, 4 H); 3.64 (m, 2 H); 3.24 (m, 2 H); 3.13 (m, 1 H); 2.40 (m, 4 H); 1.47 (s, 3 H) and 1.46 (s, 3 H)

Aufarbeitung

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashing with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by column chromatography (Si—PCC, MeOH:DCM, 0-15%)

Quellen und Nachweise

ORD-Eintrag
ord-29139050e4284c3c8d26615d2413a732
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

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