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Ammonia → HCID 66604465, Verbindung

HRID 2410863
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2410863
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.CC([O-])=O.[K+].Br[C:39]1[CH:40]=[C:41]([C:58]([NH2:60])=[O:59])[C:42]2[NH:43][C:44]3[CH:45]=[C:46]([N:52]4[CH2:57][CH2:56][O:55][CH2:54][CH2:53]4)[CH:47]=[CH:48][C:49]=3[C:50]=2[N:51]=1.CC1(C)C(C)(C)OB(C2C=CC(CN3CCOCC3)=NC=2)O1.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O.N>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O.COCCOC>[O:55]1[CH2:56][CH2:57][N:52]([C:46]2[CH:47]=[CH:48][C:49]3[C:50]4[N:51]=[C:39]([C:2]5[CH:7]=[N:6][C:5]([CH2:8][N:9]6[CH2:14][CH2:13][O:12][CH2:11][CH2:10]6)=[CH:4][CH:3]=5)[CH:40]=[C:41]([C:58]([NH2:60])=[O:59])[C:42]=4[NH:43][C:44]=3[CH:45]=2)[CH2:53][CH2:54]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

13

Edukt 8

HCID 222AmmoniaHCID 6422Trifluoroacetic acid2×HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 120852844-((5-Bromopyridin-2-yl)methyl)morpholine
HCID 57416470
4-{[5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]methyl}morpholine
HCID 86663061HCID 86663061, Verbindung

Produkt 1

HCID 66604465HCID 66604465, VerbindungAusbeute 35,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418807HCID 178418807, VerbindungKatalysator2×HCID 887MethanolLösungsmittel3×HCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A microwave vial containing a mixture of 4-((5-bromopyridin-2-yl)methyl)morpholine (537 mg, 2.09 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (583 mg, 2.30 mmol), KOAc (410 mg, 4.18 mmol) and PdCl2(dppf)-CH2Cl2 adduct (85 mg, 0.10 mmol) was flushed with nitrogen, dioxane (5 mL) was added. and the vial was sealed and heated at 100° C. for 6 hr. The reaction was filtered and the solid was washed with EtOAc. The filtrate was and washed with water, brine, and dried over MgSO4. Removal of the solvent left 750 mg of crude 4-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)methyl)morpholine (750 mg) as a brown thick oil that was used as such. A microwave vial containing a mixture of 2-bromo-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (60 mg, 0.14 mmol), 4-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)methyl)morpholine (130 mg, 0.171 mmol), PdCl2(dppf)-CH2Cl2 adduct (12 mg, 0.014 mmol) was flushed with nitrogen. DME (2.5 mL) and Na2CO3 (0.36 mL, 0.72 mmol, 2.0 M aq. solution) were added and the vial was sealed and heated at 100° C. for 5 hr. Preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA; gradient of 0 to 60% B over 10 min at 42 mL/min) followed by SCX capture and release with 2 N NH3 in MeOH gave 7-morpholino-2-(6-(morpholinomethyl)pyridin-3-yl)-5H-pyrido[3,2-b]indole-4-carboxamide (25 mg, 0.050 mmol, 35% yield) as a solid. MS (ESI) m/z 473.21 (M+H). 1H NMR (500 MHz, Acetone) δ ppm 10.75 (1H, s), 9.36 (1H, d, J=2.14 Hz), 8.58 (1H, dd, J=8.09, 2.29 Hz), 8.35 (1H, s), 8.10-8.22 (2H, m), 7.62 (1H, d, J=7.93 Hz), 7.29 (1H, d, J=2.14 Hz), 7.18 (1H, br. s.), 7.07 (1H, dd, J=8.85, 2.14 Hz), 3.80-3.87 (4H, m), 3.71 (2H, s), 3.64-3.69 (4H, m), 3.28-3.35 (4H, m), 2.47-2.57 (4H, m).

Aufarbeitung

  1. additionA microwave vial containing
  2. customwas flushed with nitrogen, dioxane (5 mL)
  3. additionwas added
  4. customand the vial was sealed
  5. filtrationThe reaction was filtered
  6. washthe solid was washed with EtOAc
  7. washwashed with water, brine
  8. dry with materialdried over MgSO4
  9. customRemoval of the solvent
  10. waitleft 750 mg of crude 4-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)methyl)morpholine (750 mg) as a brown thick oil that
  11. additionA microwave vial containing
  12. customwas flushed with nitrogen
  13. customthe vial was sealed
  14. temperatureheated at 100° C. for 5 hr

Quellen und Nachweise

ORD-Eintrag
ord-e26b7a1625024dcd929fb549d604290b
Quelldatensatz
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08815840B2

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