Cesium carbonate → HCID 56952518, compound

HRID 2366301Notes

Reaction equation

HRID 2366301 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]([Br: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]>[Br:19][C:5]1[C:6]2[N:10]=[C:9]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[S:8][C:7]=2[C:2]([NH:27][C:23]2[CH:22]=[C:21]([CH3:20])[N:26]=[CH:25][N:24]=2)=[N:3][CH:4]=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 86669025HCID 86669025, compound

Product 1

HCID 56952518HCID 56952518, compoundYield 78.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
75 °C

Procedure

The mixture of 4,7-dibromo-2-(2-chloro-6-fluoro-phenyl)thiazolo[5,4-c]pyridine (0.227 mmol; 96 mg), 6-methylpyrimidin-4-amine (0.34 mmol, 37 mg), Pd2(dba)3 (0.011 mmol, 10 mg), XantPhos (0.0227 mmol; 14 mg) and Cs2CO3 (0.4544 mmol, 148 mg) in 1,4-dioxane (3 mL) was heated at 75° C. under nitrogen in an oil bath for 4.5 hours. The reaction mixture was then cooled to room temperature, filtered through celite, washed with EtOAc. The filtrate was concentrated and the resulting crude product was purified by silica gel chromatography (30-100% EtOAc/hexane) to give the title compound as an off-white solid (80 mg, 78% yield). 1H NMR (400 MHz, DMSO-d6) δ 10.76 (s, 1H), 8.64 (s, 1H), 8.59 (s, 1H), 7.77-7.68 (m, 1H), 7.62 (d, J=8.1 Hz, 1H), 7.56-7.48 (m, 2H), 2.39 (s, 3H). LCMS (Method B): RT=4.39 min, m/z 450.0 [M+H+].

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. filtrationfiltered through celite
  3. washwashed with EtOAc
  4. concentrationThe filtrate was concentrated
  5. customthe resulting crude product was purified by silica gel chromatography (30-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-1a422b5a46324a97aaf99a7b40385a82
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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