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Sodium Carbonate → HCID 89908303, Verbindung

HRID 924039
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 924039
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:27][C@@H:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:32]3[CH:33]=[N:28][CH:29]=[N:30][CH:31]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 86702604(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide

Produkt 1

HCID 89908303HCID 89908303, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, Verbindung
Katalysator
HCID 80711,2-DimethoxyethaneLösungsmittel
HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(R)-5-Bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide (Stage 186.1, 92 mg, 0.2 mmol) and pyrimidin-5-ylboronic acid (49.6 mg, 0.4 mmol) were dissolved in DME (0.8 mL). A solution of 2 M Na2CO3 (0.300 mL, 0.6 mmol) was added, the mixture was flushed with argon, heated to 100° C. in a pressure safe vial, then Pd(PPh3)2Cl2 (14 mg, 0.02 mmol) was added. The RM was stirred under argon at 80-90° C. for 2 h. After cooling at RT, the RM was dissolved in EtOAc and washed with brine. The organic phase was dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue that was purified by flash chromatography (RediSep® Silica gel column, (DCM/MeOH 98:2)/MeOH, from 0 to 5% MeOH) and treated with Si-Thiol (80 mg) in MeOH to afford the title compound as a beige crystalline powder. HPLC (Condition 4) tR=5.02 min, HPLC Chiral (CHIRALPAK® AD-H, 250×4.6 mm, 5 μm, eluent: EtOH/MeOH (50:50), 1 mL/min, UV 220 nm, tR=10.32 min, UPLC-MS (Condition 3) tR=1.00 min, m/z=462.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.79 (m, 1H) 1.78-1.91 (m, 1H) 2.87 (d, J=1.00 Hz, 1H) 3.21 (m, J=6.60 Hz, 2H) 3.32-3.42 (m, 1H) 4.14-4.24 (m, 1H) 4.87 (d, J=3.13 Hz, 1H) 7.68 (d, J=8.60 Hz, 2H) 7.90 (d, J=8.60 Hz, 2H) 8.09 (d, J=1.95 Hz, 1H) 8.76-8.80 (m, 1H) 8.88 (s, 2H) 9.18 (s, 1H) 10.26 (s, 1H).

Aufarbeitung

  1. customthe mixture was flushed with argon
  2. temperatureAfter cooling at RT
  3. washwashed with brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue that
  7. customwas purified by flash chromatography (RediSep® Silica gel column, (DCM/MeOH 98:2)/MeOH, from 0 to 5% MeOH)
  8. additiontreated with Si-Thiol (80 mg) in MeOH

Quellen und Nachweise

ORD-Eintrag
ord-fa13b621dddf42849316df3234f22868
Quelldatensatz
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09278981B2

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