Dimethylformamide → 5-[({[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}amino)-methyl]pyrrolidin-2-one

HRID 1040114

Reaktionsgleichung

Reaktionsgleichung von HRID 1040114
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([CH:24]=O)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[NH2:26][CH2:27][CH:28]1[NH:32][C:31](=[O:33])[CH2:30][CH2:29]1.CN(C=O)C.C([BH3-])#N.[Na+]>C(O)(=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([CH2:24][NH:26][CH2:27][CH:28]3[NH:32][C:31](=[O:33])[CH2:30][CH2:29]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:17])([F:16])[F:18])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 5003444Sodium cyanoborohydrideHCID 141431895-(Aminomethyl)pyrrolidin-2-oneHCID 866582525-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carbaldehyde

Produkt 1

HCID 584562135-[({[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}amino)-methyl]pyrrolidin-2-oneAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

To a flask was added 4 Å molecular sieves (200 mgs) and the product from Step 1 (0.050 g, 0.14 mmol), 5-(aminomethyl)pyrrolidin-2-one (0.016 g, 0.21 mmol) and a 95:5 solution of DMF: acetic acid (1.4 mL). The mixture was stirred overnight. Resin-bound sodium cyanoborohydride (0.44 g, 0.41 mmol, 0.93 mmol/g loading) was added and the reaction was stirred for 72 hours. The mixture was filtered and purified by reverse phase HPLC (12-100% acetonitrile gradient with water over 6 minutes with 0.1% formic acid buffer) to yield 5-[({[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}amino)-methyl]pyrrolidin-2-one (0.016 g, 25%). MS ESI: [M+H]+ m/z 463.1. 1H NMR (600 MHz, DMSO-d6) δ 10.22 (s, 1H), 8.81 (d, J=5.2, 1H), 7.96 (s, 2H), 7.61 (s, 1H), 7.42 (s, 1H), 7.26 (d, J=5.1, 1H), 7.14 (s, 1H), 4.03 (s, 2H), 3.63 (s, 1H), 2.74-2.53 (m, 1H), 2.47 (m, 1H), 2.29 (s, 3H), 2.20-1.98 (m, 3H), 1.80-1.59 (m, 1H). rhSYK activity=+++

Aufarbeitung

  1. additionTo a flask was added 4 Å molecular sieves (200 mgs)
  2. stirringthe reaction was stirred for 72 hours
  3. filtrationThe mixture was filtered
  4. custompurified by reverse phase HPLC (12-100% acetonitrile gradient with water over 6 minutes with 0.1% formic acid buffer)

Quellen und Nachweise

ORD-Eintrag
ord-7f2f66624f0c476998d96b8414cbf8ea
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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