Acetic Acid → 2-((2-Chloro-5-cyano-3-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 1430946

Reaktionsgleichung

Reaktionsgleichung von HRID 1430946
[Cl:1][C:2]1[C:7]([CH:8]=O)=[CH:6][C:5]([C:10]#[N:11])=[CH:4][C:3]=1[NH:12][C:13]1[N:18]=[C:17]([NH:19][CH:20]2[CH2:22][CH2:21]2)[C:16]2=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:15]2[N:14]=1.[CH3:28][S:29]([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)(=[O:31])=[O:30].COC(OC)OC.C(O)(=O)C.C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>CO.C(Cl)Cl.C1COCC1>[Cl:1][C:2]1[C:7]([CH2:8][N:35]2[CH2:36][CH2:37][N:32]([S:29]([CH3:28])(=[O:31])=[O:30])[CH2:33][CH2:34]2)=[CH:6][C:5]([C:10]#[N:11])=[CH:4][C:3]=1[NH:12][C:13]1[N:18]=[C:17]([NH:19][CH:20]2[CH2:22][CH2:21]2)[C:16]2=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:15]2[N:14]=1

Komponenten

10

Edukt 6

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 516892Sodium BicarbonateHCID 7091611-(Methylsulfonyl)piperazineHCID 5003444Sodium cyanoborohydride2×HCID 867086482-((2-Chloro-5-cyano-3-formylphenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Produkt 1

HCID 867086502-((2-Chloro-5-cyano-3-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileAusbeute 31,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of 2-((2-chloro-5-cyano-3-formylphenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 400) (18 mg, 0.048 mmol), 1-(methylsulfonyl)piperazine (9.5 mg, 0.058 mmol), trimethylorthoformate (0.027 mL, 0.242 mmol), and acetic acid (3 μL, 0.05 mmol) in a mixture of MeOH (0.5 mL) and DCM (0.5 mL) was stirred at RT for 15 min. A solution of sodium cyanoborohydride (0.097 mL, 1M in THF mL, 0.097 mmol) was added and the reaction was left stirring at RT overnight. Additional sodium cyanoborohydride (0.097 mL, 1M in THF mL, 0.097 mmol) was added and the reaction was left stirring for 1 day. A saturated aq. solution of NaHCO3 solution was added and, after 15 min, this was extracted with a mixture of 5% MeOH in DCM (5×). The combined organic extracts were dried with sodium sulfate and the solvent was removed. Silica gel radial chromatography of the residue eluting with DCM containing 0 to 2% MeOH afforded the title compound (7.9 mg) as a foam.

Aufarbeitung

  1. waitthe reaction was left
  2. stirringstirring at RT overnight
  3. waitthe reaction was left
  4. stirringstirring for 1 day
  5. extractionthis was extracted with a mixture of 5% MeOH in DCM (5×)
  6. dry with materialThe combined organic extracts were dried with sodium sulfate
  7. customthe solvent was removed
  8. washSilica gel radial chromatography of the residue eluting with DCM containing 0 to 2% MeOH

Quellen und Nachweise

ORD-Eintrag
ord-882df63b3ced4fdc8adfe262361d94f3
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940736B2

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