Sodium Carbonate → HCID 86716501, compound

HRID 1501329Notes

Reaction equation

HRID 1501329 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:21][CH2:20][CH2:19]4)=[CH:14][CH:13]=3)[N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[N:36]1[CH:41]=[CH:40][CH:39]=[C:38](B(O)O)[CH:37]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:8][C:6]1[CH:7]=[C:2]([C:38]2[CH:37]=[N:36][CH:41]=[CH:40][CH:39]=2)[C:3]2[N:4]([C:9]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:21][CH2:20][CH2:19]4)=[CH:14][CH:13]=3)[N:11]=2)[N:5]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 86716502HCID 86716502, compound

Product 1

HCID 86716501HCID 86716501, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl {1-[4-(8-bromo-6-chloro-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-7.1 (0.15 g, 0.27 mmol), 3-pyridineboronic acid (0.040 g, 0.33 mmol, 1.2 equiv.), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (0.022 g, 0.03 mmol, 0.1 equiv.), Na2CO3 (0.086 g, 0.81 mmol, 3.0 equiv.), in dioxane (2.9 mL) and water (0.4 mL) was bubbled with Ar, then placed under an argon atmosphere and was irradiated in a microwave apparatus at 105° C. for 90 min. The reaction mixture was then added to a mixture of water (10 mL), a saturated aqueous NH4Cl solution (10 mL) and CH2Cl2 (20 mL). The resulting mixture was stirred strongly for 30 minutes. The organic phase was separated, dried (Na2SO4 anh), and concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 1.0 min, 80% hexane/20% EtOAc 3.0 min, gradient to 50% hexane/50% EtOAc 2.5 min, 50% hexane/50% EtOAc 3.5 min, gradient to 100% EtOAc 3.0 min, 100% EtOAc 4.8 min) to give tert-butyl (1-{4-[6-chloro-3-phenyl-8-(pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate (0.046 g, 31%):

Workup

  1. customwas prepared in a manner analgous to
  2. customwater (0.4 mL) was bubbled with Ar
  3. customwas irradiated in a microwave apparatus at 105° C. for 90 min
  4. additionThe reaction mixture was then added to a mixture of water (10 mL)
  5. customThe organic phase was separated
  6. dry with materialdried (Na2SO4 anh)
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting material was purified
  9. customMPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 1.0 min, 80% hexane/20% EtOAc 3.0 min, gradient to 50% hexane/50% EtOAc 2.5 min, 50% hexane/50% EtOAc 3.5 min, gradient to 100% EtOAc 3.0 min, 100% EtOAc 4.8 min)

Sources & evidence

ORD record
ord-8d1e1e9f56a44ccfa88acad9dc905cb7
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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