Cesium carbonate → HCID 66801413, compound

HRID 2366293Notes

Reaction equation

HRID 2366293 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])=[N:10][C:6]=2[C:5]([F:20])=[CH:4][N:3]=1.[CH3:21][C:22]1[N:27]=[CH:26][N:25]=[C:24]([NH2:28])[CH:23]=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:19][C:18]1[C:11]([C:9]2[S:8][C:7]3[C:2]([NH:28][C:24]4[CH:23]=[C:22]([CH3:21])[N:27]=[CH:26][N:25]=4)=[N:3][CH:4]=[C:5]([F:20])[C:6]=3[N:10]=2)=[C:12]([CH:15]=[CH:16][CH:17]=1)[C:13]#[N:14]

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 86669020HCID 86669020, compound

Product 1

HCID 66801413HCID 66801413, compoundYield 36.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(4-bromo-7-fluorothiazolo[5,4-c]pyridin-2-yl)-3-chlorobenzonitrile (0.110 g, 0.30 mmol), 6-methylpyrimidin-4-ylamine (35 mg, 0.32 mmol), XantPhos (0.018 g, 0.03 mmol) and Cs2CO3 (247 mg, 0.75 mmol) in dioxane (2.5 mL) was degassed with a stream of argon. Pd2(dba)3 (0.014 g, 0.015 mmol) was added and the reaction mixture was heated at 80° C. for 2 hours in a sealed vial. After cooling to room temperature, the crude reaction mixture was filtered through Celite® washing with EtOAc (50 mL). The filtrate was concentrated to dryness under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-100% EtOAc in DCM, then triturated with diethyl ether (×2), to afford the title compound as a pale yellow solid (43 mg, 36% yield). 1H NMR (400 MHz, CDCl3): δ 8.73 (d, J=1.2 Hz, 1H), 8.34 (d, J=1.8 Hz, 1H), 7.86-7.76 (m, 3H), 7.66 (t, J=8.0 Hz, 1H), 7.57 (br s, 1H), 2.56 (s, 3H). LCMS (Method C): RT=3.31 min, m/z: 397 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. temperatureAfter cooling to room temperature
  3. customthe crude reaction mixture
  4. filtrationwas filtered through Celite®
  5. washwashing with EtOAc (50 mL)
  6. concentrationThe filtrate was concentrated to dryness under reduced pressure
  7. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-100% EtOAc in DCM
  8. customtriturated with diethyl ether (×2)

Sources & evidence

ORD record
ord-4b6135428d5a4f7092a735586de2516a
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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