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

HRID 733732Notes

Reaction equation

HRID 733732 reaction equation
[Cl:1][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.[Cl:20][C:21]1[CH:27]=[C:26]([C:28]#[N:29])[CH:25]=[CH:24][C:22]=1[NH2:23].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.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]>[ClH:1].[Cl:20][C:21]1[CH:27]=[C:26]([CH:25]=[CH:24][C:22]=1[NH:23][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:28]#[N:29]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 5198964-Amino-3-chlorobenzonitrileHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)3×HCID 578410404-Chloro-1-methyl-7-(4-morpholinylcarbonyl)-1H-pyrrolo[3,2-c]pyridine

Product 1

HCID 688672333-Chloro-4-{[1-methyl-7-(4-morpholinylcarbonyl)-1H-pyrrolo[3,2-c]pyridin-4-yl]amino}benzonitrile hydrochlorideYield 17.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst3×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-1-methyl-7-(4-morpholinylcarbonyl)-1H-pyrrolo[3,2-c]pyridine (100 mg), 2-chloro-4-cyanoaniline (60 mg), cesium carbonate (168 mg), tris(dibenzylideneacetone)dipalladium (0) (15 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (10 mg) in 1,4-dioxan (2 ml) was heated to 100° C. under nitrogen for 2 h. Added tris(dibenzylideneacetone)dipalladium (0) (15 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (10 mg) and continued heating at 100° C. under nitrogen over night. Added tris(dibenzylideneacetone)dipalladium (0) (15 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (10 mg) and continued heating at 100° C. under nitrogen over night. The reaction mixture was diluted with dichloromethane and washed with water then dried (MgSO4), filtered and evaporated. Purified by trituration with 1:1 methanol:DMSO washing the filtered solid with methanol. Salt formation was as described in Example 101 to afford the title compound as a pale yellow solid (27 mg).

Workup

  1. washwashed with water
  2. dry with materialthen dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customPurified by trituration with 1:1 methanol

Sources & evidence

ORD record
ord-55d3572364b04bc7bc747f36e892edfa
Source dataset
uspto-grants-2009_09
Patent number
US07589206B2

Reaction notes

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