Cesium carbonate → HCID 66801826, compound

HRID 2366279Notes

Reaction equation

HRID 2366279 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:18]([Cl:19])=[CH:17][C:14]([C:15]#[N:16])=[CH:13][C:12]=3[Cl:20])=[N:10][C:6]=2[C:5]([F:21])=[CH:4][N:3]=1.[CH3:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]([NH2:29])[CH:24]=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:72]([O-])([O-:74])=[O:73].[Cs+].[Cs+]>O1CCOCC1.CO.O.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].C(O)=O>[CH:72]([OH:74])=[O:73].[Cl:20][C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([Cl:19])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:29][C:25]3[CH:24]=[C:23]([CH3:22])[N:28]=[CH:27][N:26]=3)=[N:3][CH:4]=[C:5]([F:21])[C:6]=2[N:10]=1)[C:15]#[N:16]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86669013HCID 86669013, compound

Product 1

HCID 66801826HCID 66801826, compoundYield 30%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 284Formic AcidSolventHCID 312751,4-DioxaneSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(4-bromo-7-fluorothiazolo[5,4-c]pyridin-2-yl)-3,5-dichlorobenzonitrile (0.128 g, 0.318 mmol), 6-methylpyrimidin-4-ylamine (0.033 g, 0.35 mmol), XantPhos (0.019 g, 0.032 mmol) and Cs2CO3 (0.207 g, 0.635 mmol) in dioxane (4 mL) was degassed with a stream of argon. Pd2(dba)3 (0.015 g, 0.016 mmol) was added and the reaction mixture was heated at 80° C. for 18 hours. After cooling to room temperature, the crude reaction mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×2) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-5% MeOH in DCM and then by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 30 minute gradient 40-90%, 0.1% HCO2H in MeOH/H2O) to afford the title compound as an off-white solid (44 mg, 30% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.72 (s, 1H), 8.61 (d, J=1.1 Hz, 1H), 8.50 (d, J=1.8 Hz, 1H), 8.40 (s, 2H), 8.31 (s, 1H), 7.39 (s, 1H), 2.38 (s, 3H). LCMS (Method C): RT=3.71 min, m/z: 431 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. temperatureAfter cooling to room temperature
  3. customthe crude reaction mixture
  4. customwas partitioned between EtOAc and water
  5. extractionThe aqueous phase was extracted with EtOAc (×2)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-c6913d26a6ca4680813027fe8c692a6e
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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