Phosphorus oxychloride → (S)-tert-butyl 1-((5-(5-(2-methoxybenzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamate

HRID 2196516Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2196516
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:31])[C:10]([NH:12][CH2:13][C:14]1[S:18][C:17]([N:19]2[C:23]([C:24](O)=[O:25])=[CH:22][C:21]([C:27]([F:30])([F:29])[F:28])=[N:20]2)=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:32][O:33][C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36][NH2:37].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[CH3:32][O:33][C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36][NH:37][C:24]([C:23]1[N:19]([C:17]2[S:18][C:14]([CH2:13][NH:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[CH3:31])=[CH:15][CH:16]=2)[N:20]=[C:21]([C:27]([F:29])([F:30])[F:28])[CH:22]=1)=[O:25]

Komponenten

5

Edukt 3

HCID 24813Phosphorus oxychlorideHCID 812922-MethoxybenzylamineHCID 69298544HCID 69298544, Verbindung

Produkt 1

HCID 69097944(S)-tert-butyl 1-((5-(5-(2-methoxybenzylcarbamoyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamateAusbeute 24,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of 25 (0.059 g, 0.128 mmol) in pyridine (0.851 mL) at 0° C. was added 2-methoxybenzylamine (0.020 mL, 0.153 mmol) and followed by dropwise addition of POCl3 (0.013 mL, 0.140 mmol). The mixture was stirred for 30 min at 0° C., then for 1 h from 0° C. to 21° C., then for 16 h at room temperature. The mixture was quenched with water and extracted with ethyl acetate, washed with brine, dried (MgSO4) filtered and concentrated. The residue was purified by silica gel column chromatography with gradient of EtOAc (20-60%) in hexanes to afford 26e (18 mg, 24%) as a white solid. LRMS (ESI): calc. 581.2; found 604.3 (MNa)+.

Aufarbeitung

  1. waitfor 1 h from 0° C. to 21° C.
  2. waitfor 16 h at room temperature
  3. customThe mixture was quenched with water
  4. extractionextracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography with gradient of EtOAc (20-60%) in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-e7d1362089354254b629f80a61d06067
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08338437B2

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