Cesium carbonate → 3-Methyl-4-{[1-methyl-7-(4-morpholinylcarbonyl)-1H-pyrrolo[3,2-c]pyridin-4-yl]amino}benzonitrile

HRID 733730Notes

Reaction equation

HRID 733730 reaction equation
Cl[C:2]1[C:7]2[CH:8]=[CH:9][N:10]([CH3:11])[C:6]=2[C:5]([C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][C:22]=1[CH3:29].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.ClCCl.CO.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:29][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:21]=1[NH:20][C:2]1[C:7]2[CH:8]=[CH:9][N:10]([CH3:11])[C:6]=2[C:5]([C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][N:3]=1)[C:25]#[N:26]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70103164-Amino-3-methylbenzonitrileHCID 578410404-Chloro-1-methyl-7-(4-morpholinylcarbonyl)-1H-pyrrolo[3,2-c]pyridine

Product 1

HCID 578409723-Methyl-4-{[1-methyl-7-(4-morpholinylcarbonyl)-1H-pyrrolo[3,2-c]pyridin-4-yl]amino}benzonitrile

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-1-methyl-7-(4-morpholinylcarbonyl)-1H-pyrrolo[3,2-c]pyridine (100 mg), 4-amino-3-methylbenzonitrile (57 mg), cesium carbonate (163 mg), tris(dibenzylideneacetone)dipalladium (0) (7 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (5 mg) in 1,4-dioxan (2 ml) was heated to 100° C. under argon overnight. The reaction mixture was diluted with dichloromethane and washed with water, followed by saturated sodium chloride solution, then dried (MgSO4), filtered and evaporated. The residue was triturated with 2:1:1 methanol/dimethylsulfoxide/diethyl ether to yield an off white solid. This was dissolved in 1:1 methanol/dichloromethane and a solution of 1.0M hydrochloric acid in diethyl ether (1.4 ml) and the solvent evaporated to afford the title compound as an off white solid (36 mg).

Workup

  1. washwashed with water
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was triturated with 2:1:1 methanol/dimethylsulfoxide/diethyl ether
  6. customto yield an off white solid
  7. customa solution of 1.0M hydrochloric acid in diethyl ether (1.4 ml) and the solvent evaporated

Sources & evidence

ORD record
ord-e022c74f02864438877c4ba657b5ed89
Source dataset
uspto-grants-2009_09
Patent number
US07589206B2

Reaction notes

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