Cesium carbonate → HCID 118666212, compound

HRID 630477Notes

Reaction equation

HRID 630477 reaction equation
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.Cl[C:44]1[N:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[F:56])=[CH:46][N:45]=1.[CH3:57][C:58]1[C:66]2[C:61](=[CH:62][C:63]([C:67]([N:69]3[CH2:74][CH2:73][O:72][CH2:71][CH2:70]3)=[O:68])=[CH:64][CH:65]=2)[NH:60][CH:59]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:56][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=1[C:47]1[CH:46]=[N:45][C:44]([N:60]2[C:61]3[C:66](=[CH:65][CH:64]=[C:63]([C:67]([N:69]4[CH2:74][CH2:73][O:72][CH2:71][CH2:70]4)=[O:68])[CH:62]=3)[C:58]([CH3:57])=[CH:59]2)=[N:49][CH:48]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 463120562-Chloro-5-(2-fluorophenyl)pyrimidineHCID 118676877HCID 118676877, compound

Product 1

HCID 118666212HCID 118666212, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

Palladium(II) acetate (8 mg, 0.036 mmol) and Xantphos (42 mg, 0.072 mmol) were added under an argon atmosphere to a solution of 2-chloro-5-(2-fluorophenyl)pyrimidine (150 mg, 0.72 mmol), (3-methyl-1H-indol-6-yl)(morpholino)methanone (176 mg, 0.72 mmol; synthesized from morpholine and 3-methyl-1H-indole-6-carboxylic acid) and cesium carbonate (422 mg, 1.29 mmol) in dry THF (5 mL). The reaction mixture was heated in a microwave at 120° C. for 1 h. After cooling to room temperature, water was added and the mixture was extracted with ethyl acetate (2×15 mL). Purification by flash chromatography [silica, heptane with 25% to 75% ethyl acetate] afforded the target compound as white solid. Yield: 185 mg (62% of theory). HPLC-MS: m/z [M+H]+=417.1

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture was extracted with ethyl acetate (2×15 mL)
  3. customPurification by flash chromatography [silica, heptane with 25% to 75% ethyl acetate]

Sources & evidence

ORD record
ord-d0adfeb51e0741e588123e8b622ae63f
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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