Cesium carbonate → Methyl {5-[(5-{[(4-chlorophenyl)acetyl]amino}pyridin-3-yl)carbonyl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}acetate

HRID 82107

Reaktionsgleichung

Reaktionsgleichung von HRID 82107
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([C:18]([C:20]3[C:28]4[CH:27]=[N:26][CH:25]=[N:24][C:23]=4[NH:22][CH:21]=3)=[O:19])[CH:17]=2)=[O:10])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:36][C:37]([O:39][CH3:40])=[O:38]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:18]([C:20]3[C:28]4[CH:27]=[N:26][CH:25]=[N:24][C:23]=4[N:22]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH:21]=3)=[O:19])[CH:15]=[N:14][CH:13]=2)=[O:10])=[CH:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 708176452-(4-chlorophenyl)-N-[5-(7H-pyrrolo[2,3-d]pyrimidin-5-ylcarbonyl)pyridin-3-yl]acetamide

Produkt 1

HCID 70847670Methyl {5-[(5-{[(4-chlorophenyl)acetyl]amino}pyridin-3-yl)carbonyl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}acetateAusbeute 120,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a stirred solution of 2-(4-chlorophenyl)-N-[5-(7H-pyrrolo[2,3-d]pyrimidin-5-ylcarbonyl)pyridin-3-yl]acetamide (Example 308, 250 mg, 0.638 mmol) in DMF (4 mL) was added Cs2CO3 (374 mg, 1.15 mmol) followed by methyl bromoacetate (73 uL, 0.766 mmol). The reaction was stirred at 25° C. for 3 hours and then quenched with water (10 mL) and extracted with EtOAc (3×10 mL). The organics were combined, washed with water (10 mL) and saturated brine (10 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo to give a pale yellow oil (356 mg) which solidified on standing. Purification by column chromatography on silica gel (gradient of 0-100% 90:10:1 DCM/MeOH/NH3 in DCM) gave the title compound as a pale yellow solid in 70% yield, 208 mg. 1HNMR (400 MHz, CDCl3) δ 3.78 (s, 2H), 3.81 (s, 3H), 5.15 (s, 2H), 7.29-7.41 (m, 4H), 7.51 (s, 1H), 7.88 (s, 1H), 8.46 (m, 1H), 8.78-8.82 (m, 2H), 9.04 (s, 1H), 9.65 (s, 1H). LCMS (System 4): Rt=2.07 min; m/z 464 [M+H]+.

Aufarbeitung

  1. customquenched with water (10 mL)
  2. extractionextracted with EtOAc (3×10 mL)
  3. washwashed with water (10 mL) and saturated brine (10 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-4117716174b349b8a5414dae7f4f67b7
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846698B2

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