Sodium Bicarbonate → 6-(3-(2-Hydroxypropan-2-yl)pyrrolidin-1-yl)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 923939Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 923939
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][CH:24]([C:27]([OH:30])([CH3:29])[CH3:28])[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]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:31]1[CH:36]=[C:35](B(O)O)[CH:34]=[N:33][CH:32]=1.C([O-])(O)=O.[Na+]>COCCOC.CCO.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:30][C:27]([CH:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:35]3[CH:36]=[N:31][CH:32]=[N:33][CH:34]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]1)([CH3:29])[CH3:28]

Komponenten

8

Edukt 3

HCID 516892Sodium BicarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 899078115-Bromo-6-(3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Produkt 1

HCID 1181952506-(3-(2-Hydroxypropan-2-yl)pyrrolidin-1-yl)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

5-Bromo-6-(3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 113.1, 98 mg, 0.2 mmol) and pyrimidin-5-ylboronic acid (49.6 mg, 0.4 mmol) were dissolved in DME (0.8 mL) and EtOH (0.12 mL). A solution of 2 M NaHCO3 (0.3 mL, 0.6 mmol) was added, the RM was flushed with argon, then Pd(PPh3)2Cl2 (14.0 mg, 0.02 mmol) was added. The RM was stirred under argon at 95° C. for 2 h in a sealed pressure safe tube. After cooling at RT, the RM was dissolved in EtOAc, washed with brine, dried over Na2SO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2% to 5% MeOH) and treated with Si-Thiol (80 mg) in MeOH to afford the title compound as a white solid. HPLC (Condition 4) tR=4.94 min, UPLC-MS (Condition 3) tR=1.01 min, m/z=532.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 0.90-1.08 (m, 6H) 1.58-1.83 (m, 2H) 1.99-2.15 (m, 1H) 3.05-3.23 (m, 3H) 3.25-3.35 (m, 1H) 4.29 (s, 1H) 7.33 (d, J=8.60 Hz, 2H) 7.75-7.87 (m, 2H) 8.07 (d, J=2.35 Hz, 1H) 8.77 (d, J=2.35 Hz, 1H) 8.87 (s, 2H) 9.17 (s, 1H) 10.14 (s, 1H).

Aufarbeitung

  1. customthe RM was flushed with argon
  2. temperatureAfter cooling at RT
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness under reduced pressure
  6. customThe crude product was purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2% to 5% MeOH)
  7. additiontreated with Si-Thiol (80 mg) in MeOH

Quellen und Nachweise

ORD-Eintrag
ord-a252b90c489d461fbb690113f7204062
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278981B2

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