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

HRID 2234719Notes

Reaction equation

HRID 2234719 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([CH:18]3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH:10]=1.[NH2:37][C:38]1[CH:48]=[CH:47]C(Br)=[CH:45][C:39]=1[C:40]([N:42]([CH3:44])[CH3:43])=[O:41]>C1COCC1.C(#N)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[NH2:37][C:38]1[CH:48]=[CH:47][C:18]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[CH:10][N:11]([S:27]([C:30]4[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=4)(=[O:28])=[O:29])[C:12]3=[N:13][CH:14]=2)=[CH:45][C:39]=1[C:40]([N:42]([CH3:43])[CH3:44])=[O:41]

Participants

5

Reactant 2

HCID 509995122-Amino-5-bromo-N,N-dimethylbenzamideHCID 57731474HCID 57731474, compound

Product 1

HCID 597001802-amino-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamideYield 71%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 22177404Acetonitrile tetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3]dioxolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (1.5 g, 3 mmol), 2-amino-5-bromo-N,N-dimethyl-benzamide 0.8, 3.3 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (110 mg, 0.2 mmol) in THF/Acetonitrile/saturated NaHCO3 (5 ml/5 ml/5 ml) was stirred at 100° C. for 4 hours. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. Silica gel chromatography of the crude using a gradient of ethyl acetate and hexane afforded 2-amino-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide (1.1 g, 71% yield). 1H NMR (500 MHz, DMSO-d6) δ 2.29 (s, 3H), 2.89 (s, 6H), 3.77 (s, 3H), 6.74 (d, 1H), 7.03 (m, 1H), 7.14 (d, 1H), 7.29 (s, 1H), 7.34-7.41 (m, 4H), 7.55 (d, 1H), 7.94 (s, 2H), 8.01 (d, 2H), 8.54 (s, 1H). MS: m/z 541.1 (M+H+).

Workup

  1. temperatureto cool down to room temperature
  2. extractionextracted with ethyl acetate (3×)
  3. extractionThe combined organic layers were extracted with brine
  4. dry with materialdried with Na2SO4
  5. customdecanted
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-254be58a930b41f39d7eb9903d369121
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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