1,8-Diazabicyclo(5.4.0)undec-7-ene → N4-(5-chlorobenzo[d][1,3]dioxol-4-yl)-N2-(2,6-dimorpholinopyridin-4-yl)pyrimidine-2,4-diamine

HRID 2237405

Reaktionsgleichung

Reaktionsgleichung von HRID 2237405
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]([NH2:13])[CH:10]=[C:9]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:8]=2)[CH2:3][CH2:2]1.Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[C:36]3[O:35][CH2:34][O:33][C:32]=3[CH:31]=[CH:30][C:29]=2[Cl:37])[CH:24]=[CH:23][N:22]=1.N12CCCN=C1CCCCC2.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Cl:37][C:29]1[CH:30]=[CH:31][C:32]2[O:33][CH2:34][O:35][C:36]=2[C:28]=1[NH:27][C:25]1[CH:24]=[CH:23][N:22]=[C:21]([NH:13][C:11]2[CH:10]=[C:9]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:8]=[C:7]([N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:12]=2)[N:26]=1

Komponenten

7

Edukt 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 426316842-chloro-N-(5-chloro-1,3-benzodioxol-4-yl)pyrimidin-4-amineHCID 575713742,6-Dimorpholin-4-ylpyridin-4-amine

Produkt 1

HCID 42644813N4-(5-chlorobenzo[d][1,3]dioxol-4-yl)-N2-(2,6-dimorpholinopyridin-4-yl)pyrimidine-2,4-diamineAusbeute 29,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

2,6-Dimorpholinopyridin-4-amine (140 mg, 0.53 mmol), 2-chloro-N-(5-chlorobenzo[d][1,3]dioxol-4-yl)pyrimidin-4-amine (150 mg, 0.53 mmol), 1,8-diazabicyclo-[5.4.0]-undec-7-ene (0.158 mL, 1.06 mmol), bis(dibenzylideneacetone)palladium(0) (45.5 mg, 0.08 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (92 mg, 0.16 mmol) were dissolved in dioxane (3 mL) and sealed into a microwave tube. The reaction was degassed, purged with nitrogen and heated at 120° C. overnight. The reaction mixture was filtered off and washed thoroughly with dichloromethane. The filtrate was concentrated to dryness, diluted with dichloromethane (15 ml), washed with water (30 ml) and brine (15 ml), dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford N4-(5-chlorobenzo[d][1,3]dioxol-4-yl)-N2-(2,6-dimorpholinopyridin-4-yl)pyrimidine-2,4-diamine (80 mg, 29.6%) as a pale beige foam. NMR Spectrum: (DMSOd6) 3.09-3.25 (m, 8H), 3.57-3.70 (m, 8H), 6.00 (s, 2H), 6.17 (d, 1H), 6.52 (s, 2H), 6.91 (d, 1H), 7.04 (d, 1H), 8.02 (d, 1H), 9.02 (s, 1H), 9.03 (s, 1H); Mass spectrum: MH+ 512.

Aufarbeitung

  1. customsealed into a microwave tube
  2. customThe reaction was degassed
  3. custompurged with nitrogen
  4. filtrationThe reaction mixture was filtered off
  5. washwashed thoroughly with dichloromethane
  6. concentrationThe filtrate was concentrated to dryness
  7. additiondiluted with dichloromethane (15 ml)
  8. washwashed with water (30 ml) and brine (15 ml)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane
  12. customThe solvent was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-234bfa398b174387ba8d819a79ae1e8b
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07718653B2

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