Cesium carbonate → methyl 1-(4-chloro-2-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

HRID 1912535Notes

Reaction equation

HRID 1912535 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]2[NH:8][CH:9]=[CH:10][C:5]2=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[C:3]=1[C:18]([O:20][CH3:21])=[O:19].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Br)=[C:31]([F:37])[CH:30]=1.[NH4+].[Cl-]>CN(C)C=O.CCOC(C)=O>[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33][N:8]2[C:6]3=[N:7][C:2]([CH3:1])=[C:3]([C:18]([O:20][CH3:21])=[O:19])[C:4]([C:11]4[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=4)=[C:5]3[CH:10]=[CH:9]2)=[C:31]([F:37])[CH:30]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 27365514-Chloro-2-fluorobenzyl bromideHCID 71209360methyl 6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

Product 1

HCID 71209420methyl 1-(4-chloro-2-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylateYield 55.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

Methyl 6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (300 mg, 1.070 mmol) (example 1 step F) was dissolved in N,N-dimethylformamide (DMF) (10.700 ml). Cesium carbonate (418 mg, 1.284 mmol) and 4-chloro-2-fluorobenzyl bromide (263 mg, 1.177 mmol) were added to the solution. The reaction was set to stir at 65° C. overnight. The reaction was worked up by adding a saturated aqueous solution of NH4Cl followed by EtOAc. The layers were separated and the organic fraction was washed with water and brine. The reaction was dried over sodium sulfate and concentrated. The crude oil was passed on silica (0-60% AcOEt/Hex) and methyl 1-(4-chloro-2-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (250 mg, 0.591 mmol, 55.2% yield) was recovered as a yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ=7.46-7.39 (m, J=8.0 Hz, 2 H), 7.35-7.26 (m, J=7.9 Hz, 2 H), 7.18 (d, J=3.5 Hz, 1 H), 7.15-7.08 (m, 2 H), 7.07-7.00 (m, 1 H), 6.43 (d, J=3.5 Hz, 1 H), 5.53 (s, 2 H), 3.67 (s, 3 H), 2.75 (s, 3 H), 2.44 (s, 3 H) LCMS (m/z) ES+=423.2 (M+1).

Workup

  1. customThe layers were separated
  2. washthe organic fraction was washed with water and brine
  3. dry with materialThe reaction was dried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-eaca9f2ab47445c6bc3b77e79a5c3fbd
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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