Cesium carbonate → 6-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indole-2-carboxylic acid methyl ester

HRID 1947461Notes

Reaction equation

HRID 1947461 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9]([OH:14])[CH:8]=2)=[O:4].Cl.Cl[C:17]1[S:18][C:19]2[C:20]([N:25]=1)=[N:21][CH:22]=[CH:23][CH:24]=2.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N.CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9]([O:14][C:17]1[S:18][C:19]3[C:20]([N:25]=1)=[N:21][CH:22]=[CH:23][CH:24]=3)[CH:8]=2)=[O:4]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 10535709methyl 6-hydroxy-1H-indole-2-carboxylateHCID 574827652-Chlorothiazolo[4,5-b]pyridine hydrochloride

Product 1

HCID 687723426-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indole-2-carboxylic acid methyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 21891449acetonitrile N,N-dimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution 6-hydroxy-1H-indole-2-carboxylic acid methyl ester (4.0 g, 21 mmol) and 2-chloro-thiazolo[4,5-b]pyridine hydrochloride (4.3 g, 21 mmol) in MeCN:DMF (4:1, 250 mL) was added Cs2CO3 (13.8 g, 42 mmol) and the reaction mixture was heated (60° C., 4 h). The reaction mixture was cooled (rt) and partitioned between EtOAc (300 mL) and saturated NH4Cl (200 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×200 mL). The organic layer was dried, filtered and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography using MeOH (0.2 M NH3):DCM (0-15%) to provide the title compound as a brown solid (3.6 g, 53%). MS (ESI): mass calcd. for C16H11N3O3S, 325.1; m/z found, 326.0[M+H]+. 1H NMR (400 MHz, DMSO-d6): 12.18 (s, 1H), 8.52 (dd, J=4.8, 1.7, 1H), 8.39 (dd, J=8.0, 1.7, 1H), 7.82 (d, J=8.7, 1H), 7.53 (d, J=2.2, 1H), 7.34 (dd, J=8.0, 4.8, 1H), 7.26 (dd, J=2.2, 0.9, 1H), 7.19 (dd, J=8.7, 2.2, 1H), 3.88 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled (rt)
  2. custompartitioned between EtOAc (300 mL) and saturated NH4Cl (200 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×200 mL)
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-a3f8599e0cc0425b96e0068d23b39da8
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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