Lithium hydroxide, monohydrate → Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

HRID 1485136Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1485136
O[Li:2].O.C[O:5][C:6](=[O:46])[CH2:7][C:8]1[CH:45]=[CH:44][CH:43]=[CH:42][C:9]=1[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[N:13]=1>C1COCC1.O.CO>[C:38]([O:37][C:35]([N:32]1[CH2:31][CH2:30][N:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:9]4[CH:42]=[CH:43][CH:44]=[CH:45][C:8]=4[CH2:7][C:6]([O-:46])=[O:5])[C:17]([C:18]([F:19])([F:20])[F:21])=[CH:16][N:15]=3)=[CH:24][CH:25]=2)[CH2:34][CH2:33]1)=[O:36])([CH3:41])([CH3:39])[CH3:40].[Li+:2]

Komponenten

6

Edukt 2

HCID 168937Lithium hydroxide, monohydrateHCID 68282913tert-Butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Produkt 1

HCID 68282842Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetateAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

LiOH.H2O (0.044 g, 1.06 mmol) was added to tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I6) (0.211 g, 0.352 mmol) in THF (10 mL), water (2.5 mL) and methanol (1 mL). The resulting mixture was allowed to stir for 3 hours at 40° C. The volatiles were removed in vacuo and the residue was diluted with EtOAc (100 mL) and 2 M aq. NaOH (100 mL). The layers were separated and the aqueous layer was extracted with EtOAc (70 mL), the organic layers were combined, washed with brine (100 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the title compound (I7) (0.195 g, 96% yield) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.02 (s, 1H), 8.61 (s, 1H), 7.64-7.55 (m, 2H), 7.26-7.14 (m, 4H), 6.97-6.91 (m, 2H), 3.65 (s, 2H), 3.50-3.41 (m, 4H), 3.10-2.93 (m, 8H), 1.42 (s, 9H). LCMS Method C: rt 6.32 min; m/z 586.3 [M+H]+.

Aufarbeitung

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (100 mL) and 2 M aq. NaOH (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (70 mL)
  5. washwashed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-1bfa8e5896b74bd29b08a35b8261a66c
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09421205B2

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