Potassium Carbonate → 2-(2-(2-((3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)amino)pyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-morpholinoethanone

HRID 1399897Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1399897
Cl[C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[CH:9][N:8]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[O:13])[C:6]=2[N:7]=1.[CH2:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][N:21]1[CH2:30][CH:31]([OH:49])[CH2:32][NH:33][C:34]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[CH:36][N:35]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][N:21]1[CH2:30][CH:31]([OH:49])[CH2:32][NH:33][C:34]1[CH:39]=[C:38]([C:2]2[N:3]=[CH:4][C:5]3[CH:10]=[CH:9][N:8]([CH2:11][C:12]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)=[O:13])[C:6]=3[N:7]=2)[CH:37]=[CH:36][N:35]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 867292902-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-morpholinoethanoneHCID 867292911-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)amino)propan-2-ol

Produkt 1

HCID 752034082-(2-(2-((3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)amino)pyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-morpholinoethanoneAusbeute 50,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 2-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-morpholinoethanone (60 mg, 0.268 mmol) in dioxane/H2O (10 mL) was added 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)amino)propan-2-ol (120.5 mg, 0.15 mmol), Pd(dppf)Cl2 (10 mg,) and K2CO3 (72.86 mg, 0.15 mmol). The reaction mixture was heated at 100° C. under microwave conditions for 40 min. The mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water and the organic layer dried concentrated and the residue purified by pre-HPLC to give the desired compound (40 mg, Yield 29%). 1H NMR (400 MHz, MeOD) δ 9.01 (s, 1H), 8.07 (d, J=5.2 Hz, 1H), 7.61 (s, 1H), 7.57 (d, J=5.2 Hz, 1H), 7.50 (s, 1H), 7.09-7.02 (m, 4H), 6.72 (s, 1H), 5.31 (s, 1H), 4.13 (br.s, 1H), 3.77-3.40 (m, 12H), 2.91-2.85 (m, 4H), 2.74-2.62 (m, 2H). LCMS (m/z): 528.2 (M+1).

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with water
  4. customthe organic layer dried
  5. concentrationconcentrated
  6. customthe residue purified by pre-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-48058009c729456faa9555d485c42ece
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906900B2

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