Formaldehyde → 2-(2-(2-(2-((4-(1-Methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

HRID 1485263Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1485263
C=O.[NH:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[N:21]=[C:20]([CH2:22][CH2:23][C:24]4[C:29]([CH2:30][C:31]([NH2:33])=[O:32])=[CH:28][CH:27]=[CH:26][N:25]=4)[C:19]([C:34]([F:37])([F:36])[F:35])=[CH:18][N:17]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(Cl)Cl>[CH3:38][N:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[N:21]=[C:20]([CH2:22][CH2:23][C:24]4[C:29]([CH2:30][C:31]([NH2:33])=[O:32])=[CH:28][CH:27]=[CH:26][N:25]=4)[C:19]([C:34]([F:37])([F:35])[F:36])=[CH:18][N:17]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1

Komponenten

6

Edukt 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 601648082-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

Produkt 1

HCID 601648092-(2-(2-(2-((4-(1-Methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamideAusbeute 72,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Formaldehyde (37 wt % in H2O; 16.5 μL, 0.222 mmol) was added to a suspension of 2-(2-(2-(2-((4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide (32) (22 mg, 0.044 mmol) in anhydrous methanol (5 mL) under an atmosphere of nitrogen. Sodium triacetoxyborohydride (94.0 mg, 0.444 mmol) was then added in one portion and the reaction was stirred at room temperature for 2 hours. The volatiles were removed in vacuo and the residue was diluted with EtOAc (25 mL) and sat. aq. NaHCO3 (25 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×25 mL), the combined organic layers were washed with water (25 mL), brine (25 mL) and dried over Na2SO4. The solvent was removed under reduced pressure to yield a white solid. The solid was suspended in DCM (5 mL) and cyclohexane (20 mL) and filtered to afford the title compound (33) (16 mg, 72%) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.06 (s, 1H), 8.64 (s, 1H), 8.36 (dd, J=4.8, 1.7 Hz, 1H), 7.59 (dd, J=7.7, 1.2 Hz, 3H), 7.53 (s, 1H), 7.20-7.13 (m, 3H), 7.00 (s, 1H), 3.53 (s, 2H), 3.24 (s, 4H), 2.91 (d, J=10.6 Hz, 2H), 2.47-2.39 (m, 1H), 2.24 (s, 3H), 2.12-1.99 (m, 2H), 1.78-1.59 (m, 4H). LCMS Method C: rt 1.51, 1.579 min; m/z 499 [M+H]+.

Aufarbeitung

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (25 mL) and sat. aq. NaHCO3 (25 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  5. washthe combined organic layers were washed with water (25 mL), brine (25 mL)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed under reduced pressure
  8. customto yield a white solid
  9. filtrationcyclohexane (20 mL) and filtered

Quellen und Nachweise

ORD-Eintrag
ord-d8f54cab228f45e6bdfca165dc1bc860
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09421205B2

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