Cesium carbonate → 1-methyl-N-(1-methyl-3-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazole-3-sulfonamide

HRID 331068Notes

Reaction equation

HRID 331068 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:22])[CH:9]=[C:10]([C:11]3[CH:21]=[CH:20][C:14]4[O:15][CH2:16][CH2:17][N:18]([CH3:19])[C:13]=4[CH:12]=3)[C:3]=12.[CH3:23][N:24]1[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:31])=[O:30])=[N:25]1.CN(C)C1C=CC=CC=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[CH3:23][N:24]1[CH:28]=[CH:27][C:26]([S:29]([NH:32][C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[N:8]([CH3:22])[CH:9]=[C:10]([C:11]4[CH:21]=[CH:20][C:14]5[O:15][CH2:16][CH2:17][N:18]([CH3:19])[C:13]=5[CH:12]=4)[C:3]=23)(=[O:31])=[O:30])=[N:25]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 148356431-methyl-1H-pyrazole-3-sulfonamideHCID 710901456-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine

Product 1

HCID 867202961-methyl-N-(1-methyl-3-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazole-3-sulfonamideYield 22%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Alternatively, a mixture of 6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine (130 mg, 0.363 mmol), 1-methyl-1H-pyrazole-3-sulfonamide (D94) (88 mg, 0.544 mmol), 2-(dimethylamino)-2′-(dicyclohexylphosphino)biphenyl (21.42 mg, 0.054 mmol), Pd2(dba)3 (24.92 mg, 0.027 mmol), cesium carbonate (355 mg, 1.089 mmol) in 1,4-dioxane (2.7 mL) was heated at 120° C. for 55 mins using a microwave reactor. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was separated, washed with brine, dried and concentrated. The residue was then purified on silica eluting with a gradient of 0-100% ethyl acetate in cyclohexane to afford a material which was further purified by MDAP (acidic condition) to afford the title compound (35 mg). LCMS (A): m/z (M+H)+ 439, C21H22N6O3S requires 438 (acidic).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. customThe organic phase was separated
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was then purified on silica eluting with a gradient of 0-100% ethyl acetate in cyclohexane
  7. customto afford a material which
  8. customwas further purified by MDAP (acidic condition)

Sources & evidence

ORD record
ord-e1667d3a1c4845f3a73d1b3d8a5627cb
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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