Acetic Acid → (S)-(1-(6-methyl-2-(methyl(4-(2-methyl-1H-imidazol-1-yl)phenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol

HRID 1930641Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1930641
[CH3:1][C:2]1[N:3]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:15]=[C:16]([N:24]4[C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[CH2:26][C@H:25]4CO)[C:17]4[CH2:23][NH:22][CH2:21]C[C:18]=4[N:19]=3)=[CH:9][CH:8]=2)[CH:4]=[CH:5][N:6]=1.[C:35](O)(=O)[CH3:36].[CH2:39]=[O:40].[C:41]([BH3-])#N.[Na+]>CO>[CH3:21][N:22]1[CH2:36][CH2:35][C:18]2[N:19]=[C:14]([N:13]([CH3:41])[C:10]3[CH:9]=[CH:8][C:7]([N:3]4[CH:4]=[CH:5][N:6]=[C:2]4[CH3:1])=[CH:12][CH:11]=3)[N:15]=[C:16]([N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:26][C@H:25]3[CH2:39][OH:40])[C:17]=2[CH2:23]1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59333741(S)-(1-(2-(4-(2-Methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol

Produkt 1

HCID 46199433(S)-(1-(6-methyl-2-(methyl(4-(2-methyl-1H-imidazol-1-yl)phenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanolAusbeute 27,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

(S)-(1-(2-(4-(2-Methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol (49 mg, 0.11 mmol) was dissolved in methanol (3 mL). Acetic acid (6.18 μL, 0.11 mmol) was added followed by formaldehyde (0.016 mL, 0.22 mmol). The reaction mixture was allowed to stirred at room temperature for 15 minutes and sodium cyanoborohydride (13.58 mg, 0.22 mmol) was added. After 1 h the solvent was evaporated and the crude dissolved in few drops of methanol, filtered and purified by preparative HPLC to give (S)-(1-(6-methyl-2-(methyl(4-(2-methyl-1H-imidazol-1-yl)phenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol (14.80 mg, 26.2%) and (S)-(1-(6-methyl-2-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)indolin-2-yl)methanol (4.60 mg, 8.07%) were obtained as acetate salt.

Aufarbeitung

  1. customAfter 1 h the solvent was evaporated
  2. dissolutionthe crude dissolved in few drops of methanol
  3. filtrationfiltered
  4. custompurified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-02a6b51ab5cd46479b95c5a24a549bba
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188101B2

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