Dichloromethane → HCID 178506298, compound

HRID 1530553Notes

Reaction equation

HRID 1530553 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9](I)=[CH:10]3)[C:6]=2[CH:16]=1.CC1(C)C(C)(C)OB([C:25]2[C:26]([C:30]([F:33])([F:32])[F:31])=[N:27][NH:28][CH:29]=2)O1.C(Cl)Cl.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:25]4[C:26]([C:30]([F:33])([F:32])[F:31])=[N:27][NH:28][CH:29]=4)=[CH:10]3)[C:6]=2[CH:16]=1

Participants

7

Reactant 4

HCID 6344Dichloromethane2×HCID 10796Cesium carbonateHCID 5820440710-Bromo-2-iodo-5,6-dihydrobenzo[F]imidazo[1,2-D][1,4]oxazepineHCID 178431100HCID 178431100, compound2×

Product 1

HCID 178506298HCID 178506298, compoundYield 3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 9-bromo-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (750 mg, 1.91 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-1H-pyrazole (550 mg, 2.10 mmol), PdCl2dppf.DCM (156 mg, 0.19 mmol) and Cs2CO3 (1.55 g, 4.77 mmol) in dioxane (12 mL) and H2O (3 mL) was purged with argon and heated at 80° C. for 18 h. Further 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-1H-pyrazole (225 mg, 1.05 mmol) and PdCl2dppf.DCM (78 mg, 0.09 mmol) were added and the mixture heated at 85° C. for a further 24 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-5% MeOH in DCM) affording 9-Bromo-2-(3-trifluoromethyl-1H-pyrazol-4-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene as a white solid (20 mg, 3%). LCMS: RT 4.42 min [M+H]+ 399.0 and 401.0. 1H NMR (CDCl3, 400 MHz): δ 13.65 (1H, s), 8.57 (1H, d, J=2.61 Hz), 8.30 (1H, s), 7.43-7.42 (2H, m), 7.00 (1H, d, J=8.71 Hz), 4.52-4.45 (4H, m)

Workup

  1. temperaturethe mixture heated at 85° C. for a further 24 h
  2. washwas washed with MeOH
  3. washthe product eluted with 2M NH3/MeOH
  4. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-c30510155d52413c8b5359dc42851814
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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