Cesium carbonate → 6-chloro-N-(3-fluoropyridin-4-yl)-8-(1-isopropyl-1H-pyrazol-3-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943468Notes

Reaction equation

HRID 1943468 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[F:21])=[O:13])=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH:22]([N:25]1[CH:29]=[CH:28][C:27]([NH2:30])=[N:26]1)([CH3:24])[CH3:23].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].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:8][C:6]1[CH:7]=[C:2]([NH:30][C:27]2[CH:28]=[CH:29][N:25]([CH:22]([CH3:24])[CH3:23])[N:26]=2)[C:3]2[N:4]([C:9]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[F:21])=[O:13])=[CH:10][N:11]=2)[N:5]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 195767971-(propan-2-yl)-1H-pyrazol-3-amineHCID 596244958-Bromo-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 866492696-chloro-N-(3-fluoropyridin-4-yl)-8-(1-isopropyl-1H-pyrazol-3-ylamino)imidazo[1,2-b]pyridazine-3-carboxamideYield 92.5%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5A (80 mg, 0.245 mmol), 1-isopropyl-1H-pyrazol-3-amine (36.8 mg, 0.294 mmol), Pd2(dba)3 (11.23 mg, 0.012 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (7.10 mg, 0.012 mmol) and Cs2CO3 (160 mg, 0.491 mmol) in dioxane (2.0 mL) was degassed with argon. The mixture was heated at 110° C. under a nitrogen atmosphere overnight. After cooling to room temperature, the mixture was concentrated to remove dioxane and then water was added. The resulting precipitate was collected by filtration, rinsed with water and dried to give crude 48A (94 mg, 92%) as a dark brown solid. HPLC Rt=3.416 min (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 220 nm), [M+H]=415.

Workup

  1. customwas degassed with argon
  2. temperatureAfter cooling to room temperature
  3. concentrationthe mixture was concentrated
  4. customto remove dioxane
  5. additionwater was added
  6. filtrationThe resulting precipitate was collected by filtration
  7. washrinsed with water
  8. customdried

Sources & evidence

ORD record
ord-aa887ae405c9491fa7ef7c390f864061
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

Loading…