Cesium carbonate → HCID 66801709, compound

HRID 2366263Notes

Reaction equation

HRID 2366263 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])=[N:10][C:6]=2[C:5]([F:19])=[CH:4][N:3]=1.[CH3:20][C:21]1[N:26]=[CH:25][N:24]=[C:23]([NH2:27])[CH:22]=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:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:27][C:23]3[CH:22]=[C:21]([CH3:20])[N:26]=[CH:25][N:24]=3)=[N:3][CH:4]=[C:5]([F:19])[C:6]=2[N:10]=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 86669007HCID 86669007, compound

Product 1

HCID 66801709HCID 66801709, compoundYield 42.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
70 °C

Procedure

A mixture of 4-bromo-2-(2-chloro-6-fluorophenyl)-7-fluorothiazolo[5,4-c]pyridine (0.09 g, 0.25 mmol), 6-methylpyrimidin-4-ylamine (0.027 g, 0.25 mmol), XantPhos (0.015 g, 0.025 mmol) and Cs2CO3 (0.206 g, 0.625 mmol) in dioxane (2 mL) was degassed with a stream of argon. Pd2(dba)3 (0.012 g, 0.0125 mmol) was added and the reaction mixture was heated in a sealed vial at 70° C. for 5 hours. After allowing to cool to room temperature, a stream of argon was bubbled through the suspension and additional amounts of Pd2(dba)3 (0.010 g) and XantPhos (0.010 g) were added. The reaction mixture was heated at 80° C. for 18 hours. After cooling to room temperature, the crude mixture was filtered through Celite® washing with EtOAc and the filtrate was concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-100% EtOAc in pentane and then triturated with diethyl ether to afford the title compound as an off-white solid (41 mg, 42% yield). 1H NMR (400 MHz, CDCl3): δ 8.71 (s, 1H), 8.30 (d, J=1.9 Hz, 1H), 7.87 (s, 1H), 7.57-7.45 (m, 2H), 7.40 (d, J=8.2 Hz, 1H), 7.21 (t, J=8.7 Hz, 1H), 2.55 (s, 3H). LCMS (Method C): RT=3.54 min, m/z: 390 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. temperatureto cool to room temperature
  3. customa stream of argon was bubbled through the suspension and additional amounts of Pd2(dba)3 (0.010 g) and XantPhos (0.010 g)
  4. additionwere added
  5. temperatureThe reaction mixture was heated at 80° C. for 18 hours
  6. temperatureAfter cooling to room temperature
  7. filtrationthe crude mixture was filtered through Celite®
  8. washwashing with EtOAc
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-100% EtOAc in pentane
  11. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-0372a3186b3c4a11b32609a92d71b82e
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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