Potassium Phosphate, Tribasic → 6-(2-hydroxyethoxy)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 629090

Reaktionsgleichung

Reaktionsgleichung von HRID 629090
Br[C:2]1[C:3]([O:22][CH2:23][CH2:24][OH:25])=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][CH:37]=[N:38][CH:39]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:25][CH2:24][CH2:23][O:22][C:3]1[C:2]([C:34]2[CH:35]=[N:36][CH:37]=[N:38][CH:39]=2)=[CH:21][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)=[O:8])=[CH:5][N:4]=1

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 4192667Pyrimidine-5-boronic acid, pinacol esterHCID 899064145-bromo-6-(2-hydroxyethoxy)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Produkt 1

HCID 722020106-(2-hydroxyethoxy)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of 5-bromo-6-(2-hydroxyethoxy)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 52.1, 50 mg, 0.119 mmol), Pd(Ph3P)4 (14 mg, 0.012 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (37 mg, 0.178 mmol) in toluene (0.5 mL) was stirred for 15 min. at RT. K3PO4 (76 mg, 0.356 mmol) was added and the RM was stirred at 110° C. for 6 h. The RM was diluted with MeOH, filtered through a cartridge of PL-Thiol MP-Resin, and the filtrate was evaporated to dryness under reduced pressure. The residue was purified by preparative SFC (Column DEAP, from 12% to 17% in 6 min.) to afford the title compound as an off-white powder. UPLC-MS (Condition 2) tR=0.93 min, m/z=419.1 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 3.74 (q, J=4.83 Hz, 2H) 4.48 (t, J=4.71 Hz, 2H) 4.90 (t, J=5.27 Hz, 1H) 7.39 (d, J=8.66 Hz, 2H) 7.87 (d, J=8.85 Hz, 2H) 8.50 (d, J=1.51 Hz, 1H) 8.81 (s, 1H) 9.19 (s, 2H) 9.21 (s, 1H) 10.46 (s, 1H).

Aufarbeitung

  1. stirringthe RM was stirred at 110° C. for 6 h
  2. filtrationfiltered through a cartridge of PL-Thiol MP-Resin
  3. customthe filtrate was evaporated to dryness under reduced pressure
  4. customThe residue was purified by preparative SFC (Column DEAP, from 12% to 17% in 6 min.)

Quellen und Nachweise

ORD-Eintrag
ord-f243bf3fa211483cbf3acc5c4656eb5c
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315489B2

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