Ethylenediamine → 5-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylpyrazine-2-carboxamide

HRID 2363341Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2363341
[CH:1]([N:4](CC)C(C)C)([CH3:3])[CH3:2].[C:10]([CH2:12][C:13]1([N:26]2[CH:30]=[C:29]([C:31]3[CH:36]=[CH:35][N:34]=[C:33]4[N:37](COCC[Si](C)(C)C)[CH:38]=[CH:39][C:32]=34)[CH:28]=[N:27]2)[CH2:16][N:15]([C:17]2[N:18]=[CH:19][C:20]([C:23]([OH:25])=O)=[N:21][CH:22]=2)[CH2:14]1)#[N:11].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CC(N)C.C([O-])(O)=O.[Na+].C(N)CN>CN(C=O)C>[C:10]([CH2:12][C:13]1([N:26]2[CH:30]=[C:29]([C:31]3[CH:36]=[CH:35][N:34]=[C:33]4[NH:37][CH:38]=[CH:39][C:32]=34)[CH:28]=[N:27]2)[CH2:14][N:15]([C:17]2[N:18]=[CH:19][C:20]([C:23]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:25])=[N:21][CH:22]=2)[CH2:16]1)#[N:11]

Komponenten

8

Edukt 6

HCID 3301EthylenediamineHCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 711435965-{3-(cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylic acid

Produkt 1

HCID 711436005-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylpyrazine-2-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

N,N-Diisopropylethylamine (19 μL, 0.11 mmol) was added to a mixture of 5-{3-(cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylic acid (19.4 mg, 0.0365 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (19 mg, 0.044 mmol) and 2-propanamine (3.2 mg, 0.055 mmol) in DMF (1.0 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was worked up with saturated aqueous NaHCO3, and extracted with dichloromethylene (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was treated with methylene chloride (1.3 mL) and TFA (1.3 mL). The mixture was stirred at room temperature for 1.5 h., and concentrated under reduced pressure. The residue was dissolved in methanol (1.3 mL), and treated with ethylenediamine (0.086 mL, 1.3 mmol). The resulting mixture was stirred at room temperature for 2 h, and then purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=442.1. 1H NMR (400 MHz, DMSO-d6): δ 12.19 (br, 1H), 8.99 (s, 1H), 8.66 (d, J=1.4 Hz, 1H), 8.47 (s, 1H), 8.32 (d, J=5.7 Hz, 1H), 8.14 (d, J=8.4 Hz, 1H), 8.00 (d, J=1.4 Hz, 1H), 7.67 (dd, J=3.2, 2.7 Hz, 1H), 7.54 (d, J=5.5 Hz, 1H), 7.09 (dd, J=3.5, 2.7 Hz), 4.82 (d, J=10.0 Hz, 2H), 4.56 (d, J=10.0 Hz, 2H), 4.10 (m, 1H), 3.79 (s, 2H), 1.17 (d, J=6.4 Hz, 6H).

Aufarbeitung

  1. extractionextracted with dichloromethylene (3×20 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was treated with methylene chloride (1.3 mL) and TFA (1.3 mL)
  7. stirringThe mixture was stirred at room temperature for 1.5 h.
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in methanol (1.3 mL)
  10. stirringThe resulting mixture was stirred at room temperature for 2 h
  11. custompurified by RP-HPLC (pH=10)

Quellen und Nachweise

ORD-Eintrag
ord-fe27f2fedda8496f90ce9e31a86f56c8
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08691807B2

Notizen zur Reaktion

Wird geladen…