Water → 10-(6-fluoropyridin-3-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine

HRID 886319Notes

Reaction equation

HRID 886319 reaction equation
Cl[C:2]1[N:12]=[CH:11][C:10]2[O:9][CH2:8][CH2:7][N:6]3[CH:13]=[C:14]([C:16]4[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=4)[N:15]=[C:5]3[C:4]=2[CH:3]=1.C(#N)C.O.C([O-])(=O)C.[K+].[F:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][N:35]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:33][C:34]1[N:35]=[CH:36][C:37]([C:2]2[N:12]=[CH:11][C:10]3[O:9][CH2:8][CH2:7][N:6]4[CH:13]=[C:14]([C:16]5[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=5)[N:15]=[C:5]4[C:4]=3[CH:3]=2)=[CH:38][CH:39]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 5820431910-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine

Product 1

HCID 5820492710-(6-fluoropyridin-3-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

10-Chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine (85.0 mg, 0.257 mmol) dissolved in Acetonitrile (2 mL, 50 mmol) and Water (2 mL, 100 mmol) with dissolved Potassium acetate (85.5 mg, 0.871 mmol). Degas by bubbling nitrogen for 5 min. 2-Fluoropyridine-5-boronic acid (47.1 mg, 0.334 mmol) was added, then Tetrakis(triphenylphosphine)palladium(0) (4.0E1 mg, 0.035 mmol). The reaction was microwaved at 145 C 35 min, cooled to RT, and extracted with ethyl acetate. Combined organics were concentrated to give fluoro intermediate, 10-(6-fluoropyridin-3-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine, which was dissolved in 1,2-Dimethoxyethane (3.00 mL, 28.9 mmol). 10% aqueous HCl (3 mL) was added. The reaction was allowed to stir and heat at 80° C. overnight. The reaction was allowed to cool to room temperature and concentrated under reduced pressure to give 306, analyzed by rHPLC. MS: (ESI+)=390.1

Workup

  1. customDegas
  2. customby bubbling nitrogen for 5 min
  3. customThe reaction was microwaved at 145 C 35 min
  4. extractionextracted with ethyl acetate
  5. concentrationCombined organics were concentrated

Sources & evidence

ORD record
ord-0050df8f663f4ae4b3ac87e0c5b8fe33
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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