Cesium carbonate → 8-(6-tert-butyl-1H-benzimidazol-2-yl)-4-(3-chloro-pyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 1809123Notes

Reaction equation

HRID 1809123 reaction equation
[C:1]([C:5]1[CH:20]=[CH:19][C:8]2[NH:9][C:10]([C:12]3[CH:17]=[CH:16][C:15](N)=[CH:14][CH:13]=3)=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:22]1[C:40]([Cl:41])=[CH:39][C:25]2[NH:26][C:27](C3C4OCCNC=4C=CC=3)=[N:28][C:24]=2[CH:23]=1.ClC1C(Cl)=CC=CN=1.C([O-])([O-])=[O:51].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([C:5]1[CH:20]=[CH:19][C:8]2[N:9]=[C:10]([C:12]3[C:17]4[O:51][CH2:39][CH2:25][N:26]([C:27]5[C:40]([Cl:41])=[CH:22][CH:23]=[CH:24][N:28]=5)[C:16]=4[CH:15]=[CH:14][CH:13]=3)[NH:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 169882,3-Dichloropyridine2×HCID 670948938-(5,6-dichloro-1H-benzo[d]imidazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazineHCID 178440681HCID 178440681, compound

Product 1

HCID 670947318-(6-tert-butyl-1H-benzimidazol-2-yl)-4-(3-chloro-pyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazineYield 95%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

3.1 g (10 mmol) of 4-(5-tert-butyl-1H-benzo[d]imidazol-2-yl)benzenamine (compound 1a) obtained Example 1 was dissolved in 10 mL of toluene. 1.5 g (10 mmol) of 2,3-dichloropyridine (compound 8), 0.1 g (0.5 mmol) of Pd(OAc)2, 0.5 g (0.8 mmol) of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 4.6 g (14 mmol) of Cs2CO3 were added thereto and stirred at 90° C. for 12 hr. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, followed by dilution with ethyl acetate. The resulting product was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, followed by drying over magnesium sulfate and concentrating under reduced pressure. The resulting residue was subjected to column chromatography (ethyl acetate/hexane=2/3) to obtain the title compound (4.0 g, yield: 95%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. washThe resulting product was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution
  4. dry with materialby drying over magnesium sulfate
  5. concentrationconcentrating under reduced pressure

Sources & evidence

ORD record
ord-9ef2921affe24140baf3616265a1f7b1
Source dataset
uspto-grants-2013_01
Patent number
US08362012B2

Reaction notes

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