Potassium Carbonate → N-(4-(Chlorodifluoromethoxy)phenyl)-6-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl)-5-(4-methylpyrimidin-5-yl)nicotinamide

HRID 924143Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 924143
[Cl:1][C:2]([F:28])([F:27])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:26])[C:12]2[CH:17]=[C:16](I)[C:15]([N:19]3[CH2:23][C@@H:22]([OH:24])[C@H:21]([OH:25])[CH2:20]3)=[N:14][CH:13]=2)=[CH:6][CH:5]=1.[CH3:29][C:30]1[C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][N:33]=[CH:32][N:31]=1.C([O-])([O-])=O.[K+].[K+]>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>[Cl:1][C:2]([F:28])([F:27])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:26])[C:12]2[CH:17]=[C:16]([C:35]3[C:30]([CH3:29])=[N:31][CH:32]=[N:33][CH:34]=3)[C:15]([N:19]3[CH2:23][C@@H:22]([OH:24])[C@H:21]([OH:25])[CH2:20]3)=[N:14][CH:13]=2)=[CH:6][CH:5]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 66521319(4-Methylpyrimidin-5-yl)boronic acid pinacol esterHCID 89906772N-(4-(chlorodifluoromethoxy)phenyl)-6-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl)-5-iodonicotinamide

Produkt 1

HCID 118195116N-(4-(Chlorodifluoromethoxy)phenyl)-6-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl)-5-(4-methylpyrimidin-5-yl)nicotinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178418397HCID 178418397, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

N-(4-(chlorodifluoromethoxy)phenyl)-6-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl)-5-iodonicotinamide (Stage 282.1, 100 mg, 0.190 mmol) and 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (Stage 297.1, 62.8 mg, 0.285 mmol), Pd(Ph3P)4 (21.98 mg, 0.019 mmol) and K2CO3 (79 mg, 0.571 mmol) were added to a vial and flushed with argon. DMF (2 mL) was added and the mixture was stirred at 100° C. for 2 h. The solvent was evaporated off under reduced pressure. The crude product was dissolved in MeOH, filtered through a PL-resin Si-Thiol cartridge, the cartridge was washed with MeOH and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 14-25% to 55% MeCN in 20 min) and followed by preparative SFC (Column Diol, from 20% to 25% in 6 min). The purified product was lyophilized in water/min vol. MeCN to afford the title product as a white powder. UPLC-MS (Condition 3), tR=0.86 min, m/z=492.2/494.2 [M+H]+.

Aufarbeitung

  1. customflushed with argon
  2. additionDMF (2 mL) was added
  3. customThe solvent was evaporated off under reduced pressure
  4. dissolutionThe crude product was dissolved in MeOH
  5. filtrationfiltered through a PL-resin Si-Thiol cartridge
  6. washthe cartridge was washed with MeOH
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give a residue which
  9. customwas purified by preparative HPLC (Condition 14-25% to 55% MeCN in 20 min)
  10. customfollowed by preparative SFC (Column Diol, from 20% to 25% in 6 min)

Quellen und Nachweise

ORD-Eintrag
ord-23b51870549c46d6bdf4ee479c2a7ce9
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278981B2

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