Diisopropylethylamine → N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine

HRID 1842793Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1842793
Cl.Cl.[CH3:3][N:4]([CH3:9])[CH:5]1[CH2:8][NH:7][CH2:6]1.F[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]2[N:26]=[C:25]([C:27]3[CH:28]=[N:29][N:30]4[CH2:35][CH2:34][CH2:33][CH2:32][C:31]=34)[CH:24]=[CH:23][N:22]=2)=[C:13]([O:36][CH3:37])[CH:12]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:3][N:4]([CH3:9])[CH:5]1[CH2:8][N:7]([C:11]2[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]3[N:26]=[C:25]([C:27]4[CH:28]=[N:29][N:30]5[CH2:35][CH2:34][CH2:33][CH2:32][C:31]=45)[CH:24]=[CH:23][N:22]=3)=[C:13]([O:36][CH3:37])[CH:12]=2)[CH2:6]1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 22121220N,N-dimethylazetidin-3-amine dihydrochloride2×HCID 71240760N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine2×

Produkt 1

HCID 71240764N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amineAusbeute 50,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

N,N-Dimethylazetidin-3-amine dihydrochloride (Intermediate 26, 109 mg, 0.63 mmol), N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 127, 300 mg, 0.60 mmol), DIPEA (0.386 mL, 2.22 mmol) and DMA (4 mL) was sealed into a microwave tube and heated to 140° C. for 1 h in the microwave reactor. After cooling, to r.t., the mixture was part-purified by ion exchange chromatography, using an SCX column. The column was first washed with CH3OH and then the desired product was eluted from the column using 0.7M methanolic ammonia. Clean fractions were concentrated in vacuo to give an orange gum. Further purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (140 mg, 50%) as an orange solid; 1H NMR (CDCl3): 1.90-1.98 (2H, m), 2.05-2.12 (2H, m), 2.20 (6H, s), 3.15-3.23 (1H, m), 3.28 (2H, t), 3.69 (2H, dd), 3.96 (3H, s), 4.18 (4H, dt), 6.03 (1H, s), 6.87 (1H, d), 7.35 (1H, s), 7.97 (1H, s), 8.31 (1H, d), 9.02 (1H, s); m/z: ES+ MH+ 465.61.

Aufarbeitung

  1. temperatureAfter cooling, to r.t.
  2. customthe mixture was part-purified by ion exchange chromatography
  3. washThe column was first washed with CH3OH
  4. washthe desired product was eluted from the column
  5. concentrationwere concentrated in vacuo
  6. customto give an orange gum
  7. customFurther purification by FCC
  8. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-70be998a1f02455e81582f8fafbebf90
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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