Methanol → HCID 70817992, compound

HRID 1501325Notes

Reaction equation

HRID 1501325 reaction equation
[C:1]1([C:7]2[N:11]3[N:12]=[C:13](Br)[CH:14]=[C:15]([O:16][CH3:17])[C:10]3=[N:9][C:8]=2[C:19]2[CH:24]=[CH:23][C:22]([C:25]3([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1[CH2:41][O:40][CH2:39]C1.C(N(CC)CC)C.C[OH:50]>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]>[C:32]([O:31][C:30]([NH:29][C:25]1([C:22]2[CH:23]=[CH:24][C:19]([C:8]3[N:9]=[C:10]4[C:15]([O:16][CH3:17])=[CH:14][C:13]([C:39]([O:40][CH3:41])=[O:50])=[N:12][N:11]4[C:7]=3[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:20][CH:21]=2)[CH2:28][CH2:27][CH2:26]1)=[O:36])([CH3:34])([CH3:35])[CH3:33]

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 86716498HCID 86716498, compound

Product 1

HCID 70817992HCID 70817992, compoundYield 85%

Reagents, catalysts & solvents 1

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

Procedure

To a solution of tert-butyl (1-{4-[3-phenyl-6-bromo-8-methoxyimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-7 (0.41 g, 0.75 mmol) in MeOH (10 mL) and THF (1 mL) in an autoclave was added 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (0.12 g, 0.15 mmol, 0.20 equiv) and triethylamine (0.11 mL, 0.82 mmol, 1.1 equiv.). The autoclave was flushed with CO (approximately 5 bar) three times, then was pressurized with CO (5.2 bar), stirred at room temperature 30 min., and briefly placed under reduced atmosphere (0.06 bar). The autoclave was then pressurized with CO (5.9 bar at 20° C.), heated to 110° C., and stirred at this temperature for 22 h. The resulting solution was concentrated under reduced pressure. The resulting material was crystallized from MeOH to give methyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-8-methoxy-3-phenylimidazo[1,2-b]pyridazine-6-carboxylate (0.34 g, 85%):

Workup

  1. customThe autoclave was flushed with CO (approximately 5 bar) three times
  2. customwas then pressurized with CO (5.9 bar at 20° C.)
  3. temperatureheated to 110° C.
  4. stirringstirred at this temperature for 22 h
  5. concentrationThe resulting solution was concentrated under reduced pressure
  6. customThe resulting material was crystallized from MeOH

Sources & evidence

ORD record
ord-c38705d197d94ad9b7d5a1ba0da8060b
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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