Cesium carbonate → HCID 66807262, compound

HRID 2366256Notes

Reaction equation

HRID 2366256 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:19][C:20](=[O:22])[CH3:21])[CH:5]=[C:6]([Cl:18])[C:7]=1[C:8]1[S:9][C:10]2[C:11](Cl)=[N:12][CH:13]=[CH:14][C:15]=2[N:16]=1.[CH3:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]([NH2:30])[CH:25]=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+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:19][C:20](=[O:22])[CH3:21])[CH:5]=[C:6]([Cl:18])[C:7]=1[C:8]1[S:9][C:10]2[C:11]([NH:30][C:26]3[CH:25]=[C:24]([CH3:23])[N:29]=[CH:28][N:27]=3)=[N:12][CH:13]=[CH:14][C:15]=2[N:16]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86723318HCID 86723318, compound

Product 1

HCID 66807262HCID 66807262, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-[3,5-dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-acetamide (0.057 g, 0.15 mmol), 6-methylpyrimidin-4-ylamine (0.020 g, 0.18 mmol), Pd2(dba)3 (0.007 g, 0.0075 mmol), XantPhos (0.017 g, 0.03 mmol) and Cs2CO3 (0.098 g, 0.30 mmol) in dioxane (2 mL) was degassed with a stream of N2 and then subjected to microwave irradiation at 150° C. for 30 minutes. After cooling to room temperature, the crude reaction mixture was partitioned between EtOAc and water. The organic layer was washed with brine, then dried (Na2SO4) and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 50-100% EtOAc in cyclohexane followed by 1% MeOH in EtOAc to afford the title compound as a pale yellow solid (21 mg, 31% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.62 (s, 1H), 10.53 (s, 1H), 8.63 (d, J=1.2 Hz, 1H), 8.44 (d, J=5.6 Hz, 1H), 7.89 (s, 2H), 7.82 (d, J=5.6 Hz, 1H), 7.61 (s, 1H), 2.39 (s, 3H), 2.13 (s, 3H). LCMS (Method C): RT=3.02 min, m/z: 445 [M+H+].

Workup

  1. customwas degassed with a stream of N2
  2. customirradiation at 150° C. for 30 minutes
  3. customthe crude reaction mixture
  4. customwas partitioned between EtOAc and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe resultant residue was purified by column chromatography on silica gel eluting with 50-100% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-dac43963850f41488618cbb66f19560d
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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