Cesium carbonate → methyl 4-(chroman-6-yl)-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

HRID 1912550Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1912550
[O:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[C:16]([C:17]([O:19][CH3:20])=[O:18])=[C:15]([CH3:21])[N:14]=[C:13]4[NH:22][CH:23]=[CH:24][C:12]=34)=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[C:35]([F:40])[CH:34]=1>CN(C)C=O.C(OCC)(=O)C>[O:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[C:16]([C:17]([O:19][CH3:20])=[O:18])=[C:15]([CH3:21])[N:14]=[C:13]4[N:22]([CH2:32][C:33]5[CH:38]=[CH:37][C:36]([F:39])=[C:35]([F:40])[CH:34]=5)[CH:23]=[CH:24][C:12]=34)=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 71209166methyl 4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

Produkt 1

HCID 71209465methyl 4-(chroman-6-yl)-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of methyl 4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (0.943 g, 2.93 mmol) in N,N-Dimethylformamide (DMF) (6.0 mL) was treated with cesium carbonate (1.906 g, 5.85 mmol) and then 4-(bromomethyl)-1,2-difluorobenzene (0.561 mL, 4.39 mmol) and the mixture was heated to 80° C. for 75 minutes. The mixture was cooled to ambient temperature, diluted with ethyl acetate and then washed with water and brine. The water that was used for washing was back extracted with ethyl acetate. The combined extracts were dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford a pale yellow residue: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.25-7.17 (m, 2 H), 7.14-6.99 (m, 3 H), 6.96 (ddd, J=2.0, 4.1, 6.2 Hz, 1 H), 6.88 (d, J=8.4 Hz, 1 H), 6.44 (d, J=3.7 Hz, 1 H), 5.45 (s, 2 H), 4.30-4.20 (m, 2 H), 3.69 (s, 3 H), 2.84 (t, J=6.4 Hz, 2 H), 2.68 (s, 3 H), 2.14-1.96 (m, 2 H); LC/MS (m/z) ES+=449 (M+1).

Aufarbeitung

  1. washwashed with water and brine
  2. washfor washing
  3. extractionwas back extracted with ethyl acetate
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (0-70% ethyl acetate/hexanes)
  8. customto afford a pale yellow residue

Quellen und Nachweise

ORD-Eintrag
ord-b1dd4b64d8ab4c7d84d0461d53772289
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08609653B2

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