Formaldehyde → 1-(2-(2-(5-Chloro-2-((4-(1-methylpiperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592381Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592381
C=O.[Cl:3][C:4]1[C:5]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2([C:34]([NH2:36])=[O:35])[CH2:33][CH2:32]2)=[N:6][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)=[N:8][CH:9]=1.[C:37](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[Cl:3][C:4]1[C:5]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2([C:34]([NH2:36])=[O:35])[CH2:32][CH2:33]2)=[N:6][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH3:37])[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)=[N:8][CH:9]=1

Komponenten

5

Edukt 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 867122971-(2-(2-(5-Chloro-2-((4-(piperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Produkt 1

HCID 732964301-(2-(2-(5-Chloro-2-((4-(1-methylpiperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

Formaldehyde (37 wt % in H2O; 14 μL, 0.19 mmol) was added to a solution of 1-(2-(2-(5-chloro-2-((4-(piperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide (7) (30 mg, 63 μmol) in MeOH (5.0 mL) under an atmosphere of nitrogen. The resulting mixture was stirred for 10 minutes at room temperature before the addition of sodium triacetoxyborohydride (53 mg, 0.25 mmol). Stirring was continued for 2.5 hours at room temperature before the volatiles were removed in vacuo and the resulting residue was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4 and the volatiles evaporated in vacuo. The residue was dissolved in acetone (0.5 mL) and petroleum benzine 40-60° C. (25 mL) was added. The resulting green precipitate was isolated by filtration and dried under high vacuum to give the title compound 8 as a green solid (8 mg, 26%); 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 7.41 (d, J=8.5 Hz, 2H), 7.34 (d, J=7.3 Hz, 1H), 7.30-7.23 (m, 3H), 7.12 (d, J=8.5 Hz, 2H), 5.55 (s, 1H), 5.25 (s, 1H), 3.13 (J m, 6H), 2.52-2.41 (m, 1H), 2.38 (s, 3H), 2.23 (t, J=11.8 Hz, 2H), 1.89 (dd, J=25.4, 12.3 Hz, 2H), 1.80 (d, J=12.3 Hz, 2H), 1.68 (s, 2H), 1.06 (s, 2H). LCMS-A: rt 4.611 min; m/z 491 [M+H]+.

Aufarbeitung

  1. customwere removed in vacuo
  2. customthe resulting residue was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over MgSO4
  7. customthe volatiles evaporated in vacuo
  8. dissolutionThe residue was dissolved in acetone (0.5 mL)
  9. additionpetroleum benzine 40-60° C. (25 mL) was added
  10. customThe resulting green precipitate was isolated by filtration
  11. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-45fb20cff24c4aa192d1fb2301d93280
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238644B2

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