Cesium carbonate → HCID 56953390, compound

HRID 2366187Notes

Reaction equation

HRID 2366187 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]([C:26]#[N:27])[CH:21]=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]([Cl:17])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:19][C:20]3[N:25]=[CH:24][N:23]=[C:22]([C:26]#[N:27])[CH:21]=3)=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 668018016-aminopyrimidine-4-carbonitrileHCID 862804124-Bromo-2-(2,6-dichlorophenyl)thiazolo[5,4-c]pyridine

Product 1

HCID 56953390HCID 56953390, compoundYield 35%

Reagents, catalysts & solvents 2

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

Procedure

To a microwave tube was added 4-bromo-2-(2,6-dichlorophenyl)thiazolo[5,4-c]pyridine (60 mg, 0.17 mmol), 6-aminopyrimidine-4-carbonitrile (0.029 g, 0.22 mmol), Pd2(dba)3 (0.013 g, 0.017 mmol), XantPhos (0.017 g, 0.034 mmol) and Cs2CO3 (0.11 g, 0.34 mmol) in dioxane (3.0 mL). The mixture was degassed with N2 for 10 minutes and then irradiated in a microwave reactor at 160° C. for 2 hours. After cooling to room temperature the solid was removed via filtration. The filtrate was concentrated under reduced pressure and the residue was purified with reverse phase column chromatography, eluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3 to give the desired product as a white solid (21 mg, 35% yield). 1H NMR (500 MHz, DMSO-d6): δ 11.43 (s, 1H), 8.91 (s, 1H), 8.54 (d, J=5.0 Hz, 1H), 8.31 (s, 1H), 8.00 (d, J=5.0 Hz, 1H), 7.76-7.67 (m, 3H). LCMS (Method B): RT=6.30 min, m/z: 399.0 [M+H+].

Workup

  1. customThe mixture was degassed with N2 for 10 minutes
  2. customirradiated in a microwave reactor at 160° C. for 2 hours
  3. customwas removed via filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified with reverse phase column chromatography
  6. washeluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3

Sources & evidence

ORD record
ord-8cbbf2a9ef254b2499f9b11e8a98fb0c
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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