Dichloromethane → 3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-2-[(pyridin-4-ylmethyl)-amino]-benzamide

HRID 2234685Notes

Reaction equation

HRID 2234685 reaction equation
[F:1][C:2]1[C:3]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)=[C:4]([CH:10]=[C:11](I)[CH:12]=1)[C:5]([N:7]([CH3:9])[CH3:8])=[O:6].[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[C:38]2[C:33](=[N:34][CH:35]=[C:36](B3OC(C)(C)C(C)(C)O3)[CH:37]=2)[N:32]([S:48]([C:51]2[CH:56]=[CH:55][C:54]([CH3:57])=[CH:53][CH:52]=2)(=[O:50])=[O:49])[CH:31]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[F:1][C:2]1[C:3]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)=[C:4]([CH:10]=[C:11]([C:36]2[CH:37]=[C:38]3[C:30]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[O:23][CH3:22])=[CH:31][N:32]([S:48]([C:51]4[CH:52]=[CH:53][C:54]([CH3:57])=[CH:55][CH:56]=4)(=[O:50])=[O:49])[C:33]3=[N:34][CH:35]=2)[CH:12]=1)[C:5]([N:7]([CH3:9])[CH3:8])=[O:6]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 160390673-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 577315523-fluoro-5-iodo-N,N-dimethyl-2-[(pyridin-4-ylmethyl)-amino]-benzamide

Product 1

HCID 577315803-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-2-[(pyridin-4-ylmethyl)-amino]-benzamideYield 22.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Crude 3-fluoro-5-iodo-N,N-dimethyl-2-[(pyridin-4-ylmethyl)-amino]-benzamide (˜1.63 mmol) from the previous step and 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (822 mg, 1.63), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1, 133 mg, 0.16 mmol), acetonitrile (8 ml) and 2 M aqueous sodium carbonate solution (4 ml) were placed in a microwave reactor and irradiated to 100° C. for 10 minutes. The reaction mixture was concentrated in vacuo and the residue partitioned between dichloromethane and water. The organic layer was dried over sodium sulfate, and concentrated. The crude product was purified by flash chromatography on silica gel (0 to 100% [10% methanol in ethyl acetate] in hexanes) to afford 236 mg (22% for 2 steps) of 3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-2-[(pyridin-4-ylmethyl)-amino]-benzamide. MS: m/z 650.3 (M+H+).

Workup

  1. customirradiated to 100° C. for 10 minutes
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue partitioned between dichloromethane and water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel (0 to 100% [10% methanol in ethyl acetate] in hexanes)

Sources & evidence

ORD record
ord-dce6b539c379412fb4bcab38843325a2
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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