(3R)-(+)-3-(Dimethylamino)pyrrolidine → 5-chloro-N-{4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-(1-methylindol-3-yl)pyrimidin-2-amine

HRID 1842742

Reaktionsgleichung

Reaktionsgleichung von HRID 1842742
[CH3:1][N:2]([CH3:8])[C@@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.[Cl:9][C:10]1[C:11]([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]([CH3:38])[CH:30]=2)=[N:12][C:13]([NH:16][C:17]2[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[C:20](F)=[CH:19][C:18]=2[O:27][CH3:28])=[N:14][CH:15]=1>CC(N(C)C)=O>[Cl:9][C:10]1[C:11]([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]([CH3:38])[CH:30]=2)=[N:12][C:13]([NH:16][C:17]2[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[C:20]([N:5]3[CH2:6][CH2:7][C@@H:3]([N:2]([CH3:8])[CH3:1])[CH2:4]3)=[CH:19][C:18]=2[O:27][CH3:28])=[N:14][CH:15]=1

Komponenten

4

Edukt 2

HCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidine2×HCID 712392825-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine4×

Produkt 1

HCID 712699515-chloro-N-{4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl}-4-(1-methylindol-3-yl)pyrimidin-2-amineAusbeute 286,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

(3R)—N,N-Dimethylpyrrolidin-3-amine (126 mg, 1.11 mmol) was added to a suspension of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 87, 215 mg, 0.50 mmol) in DMA (5 mL) and the mixture was heated in a microwave at 140° C. for 0.5 h. The mixture was then concentrated in vacuo and combined with material from the reaction below for work up. (3R)—N,N-dimethylpyrrolidin-3-amine (276 mg, 2.42 mmol) was added to a suspension of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 87, 470 mg, 1.10 mmol) in DMA (10 mL) and the mixture was heated in a microwave at 140° C. for 0.5 h. The mixture was concentrated in vacuo and combined with the material from the first procedure described above, for work-up. The combined residues were dissolved in CH2Cl2 (100 mL), and the resulting solution was washed with water (2×100 mL) and sat. brine (100 mL), and then dried (MgSO4) and concentrated in vacuo, Purification by FCC, eluting with 1-10% CH3OH in CH2Cl2 gave the title compound (747 mg, 89%) as an orange gum; m/z: ES+ M+ 522.30.

Aufarbeitung

  1. concentrationThe mixture was then concentrated in vacuo
  2. customcombined with material from the reaction below for work up
  3. temperaturethe mixture was heated in a microwave at 140° C. for 0.5 h
  4. concentrationThe mixture was concentrated in vacuo
  5. dissolutionThe combined residues were dissolved in CH2Cl2 (100 mL)
  6. washthe resulting solution was washed with water (2×100 mL) and sat. brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo, Purification by FCC
  9. washeluting with 1-10% CH3OH in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-8c0b723e265a440e93e8f04f44bab1c7
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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