Cesium carbonate → 4-[5-(3-Nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one

HRID 1028096Notes

Reaction equation

HRID 1028096 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([N:16]3[CH2:22][CH2:21][CH2:20][NH:19][C:18](=[O:23])[CH2:17]3)=[N:13][CH:12]=2)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:73]1[N:78]=[C:77]([C:79]([F:82])([F:81])[F:80])[CH:76]=[CH:75][N:74]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[N+:8]([C:6]1[CH:5]=[C:4]([C:11]2[S:15][C:14]([N:16]3[CH2:22][CH2:21][CH2:20][NH:19][C:18](=[O:23])[CH2:17]3)=[N:13][CH:12]=2)[CH:3]=[C:2]([NH:1][C:73]2[N:78]=[C:77]([C:79]([F:82])([F:81])[F:80])[CH:76]=[CH:75][N:74]=2)[CH:7]=1)([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 672367484-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one

Product 1

HCID 672417784-[5-(3-Nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

4-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (482 mg, 1.446 mmol), XantPhos (251 mg, 0.434 mmol), cesium carbonate (942 mg, 2.89 mmol), palladium(II) acetate (64.9 mg, 0.289 mmol), dioxane (10 mL) and 2-chloro-4-(trifluoromethyl)pyrimidine (0.174 mL, 1.446 mmol) were successively added in a sealable reaction tube under nitrogen. The tube was sealed and the mixture was stirred at 125° C. for 5 hours. The reaction mixture was cooled to room temperature, partitioned between 25% aqueous ammonium acetate and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate and three times with 2-methyltetrahydrofuran. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Purification via CombiFlash (ethanol/dichloromethane) afforded 4-[5-(3-nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one as an amber gum. MS APCI: [M+H]+ m/z 480.1.

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between 25% aqueous ammonium acetate and ethyl acetate
  4. extractionThe aqueous layer was extracted twice with ethyl acetate and three times with 2-methyltetrahydrofuran
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification via CombiFlash (ethanol/dichloromethane)

Sources & evidence

ORD record
ord-3589d431729c40c49775ec614e09c40a
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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