Lithium hydroxide, monohydrate → 2-(2-(2-(2-((4-(4-(tert-Butoxycarbonyl)morpholin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

HRID 1473108Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1473108
C[O:2][C:3](=[O:43])[CH2:4][C:5]1[CH:42]=[CH:41][CH:40]=[CH:39][C:6]=1[CH2:7][CH2:8][C:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][N:12]=[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]3[O:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]3)=[CH:22][CH:21]=2)[N:10]=1.O.[OH-].[Li+]>C1COCC1.O>[C:35]([O:34][C:32]([N:28]1[CH2:29][CH2:30][O:31][CH:26]([C:23]2[CH:24]=[CH:25][C:20]([NH:19][C:11]3[N:10]=[C:9]([CH2:8][CH2:7][C:6]4[CH:39]=[CH:40][CH:41]=[CH:42][C:5]=4[CH2:4][C:3]([OH:43])=[O:2])[C:14]([C:15]([F:16])([F:17])[F:18])=[CH:13][N:12]=3)=[CH:21][CH:22]=2)[CH2:27]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

Komponenten

5

Edukt 2

HCID 168937Lithium hydroxide, monohydrateHCID 71229333HCID 71229333, Verbindung

Produkt 1

HCID 682828512-(2-(2-(2-((4-(4-(tert-Butoxycarbonyl)morpholin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acidAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

tert-Butyl 2-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)morpholine-4-carboxylate (I89) (46 mg, 0.077 mmol) was dissolved in THF (2 mL), and lithium hydroxide hydrate (6.0 mg, 0.15 mmol) in water (0.5 mL) was added. After 18 hours the mixture was concentrated, diluted with water (5 mL) and the pH adjusted to 3 with 6 M HCl. The mixture was extracted with ethyl acetate (3×10 mL), and the combined organic extracts washed with brine (20 mL), dried over sodium sulfate and evaporated to give the title compound (I90) (39 mg, 85% yield) as a pale yellow syrup; 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.54 (d, J=8.4 Hz, 2H), 7.35-7.27 (m, 4H), 4.38 (d, J=10.1 Hz, 1H), 4.07-3.80 (m, 5H), 3.67 (td, J=11.7, 2.7 Hz, 1H), 3.06 (s, 4H), 2.84 (s, 2H), 1.47 (s, 9H). LCMS Method C: rt 6.49 min; m/z 587.1 [M+H]+, 531.0 [M−tBu+2H]+, 487.1 [M-Boc+2H]+; m/z 585.2 [M−H]+.

Aufarbeitung

  1. concentrationAfter 18 hours the mixture was concentrated
  2. additiondiluted with water (5 mL)
  3. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
  4. washthe combined organic extracts washed with brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-0e0ba08a929149438c514cb68cfae6f8
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012461B2

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