Cesium carbonate → HCID 59618475, compound

HRID 449925Notes

Reaction equation

HRID 449925 reaction equation
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:23])[C:10]2[C:20]([Cl:21])=[CH:19][C:13]([C:14]([N:16]([CH3:18])[CH3:17])=[O:15])=[CH:12][C:11]=2[Cl:22])[CH:5]=[CH:4][N:3]=1.[N:24]1C=CC(N)=NC=1.C[C:32]1([CH3:72])[C:58]2[C:53](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:52]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[Cl:22][C:11]1[CH:12]=[C:13]([C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:19]=[C:20]([Cl:21])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:24][C:53]([CH:58]2[CH2:32][CH2:72]2)=[O:52])[CH:7]=1)=[O:23]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 689584-AminopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86648963HCID 86648963, compound

Product 1

HCID 59618475HCID 59618475, compoundYield 296.7%

Reagents, catalysts & solvents 2

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

Procedure

To a microwave tube was added N1-(2-bromopyridin-4-yl)-2,6-dichloro-N4,N4-dimethylterephthalamide (84 mg, 0.20 mmol), pyrimidin-4-amine (38 mg, 0.40 mmol), Pd2(dba)3 (18 mg, 0.020 mmol), Xantphos (23 mg, 0.040 mmol), Cs2CO3 (131 mg, 0.40 mmol) and dioxane (1.2 mL). The mixture was degassed with N2 for 5 min and then irradiated in a microwave reactor at 140° C. for 60 min. After cooling, the reaction was filtered through Celite and concentrated under reduced pressure. The residue was dissolved in DMF and purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford the desired product (50 mg, 58% yield). 1H NMR (500 MHz, DMSO-d6): δ 8.30-8.22 (m, 2H), 7.60-7.56 (m, 3H), 3.10 (s, 3H), 3.00 (s, 3H), 1.86 (m, 1H), 0.99-0.88 (m, 4H). LCMS (ESI) m/z: 421.1 [M+H+].

Workup

  1. customThe mixture was degassed with N2 for 5 min
  2. customirradiated in a microwave reactor at 140° C. for 60 min
  3. temperatureAfter cooling
  4. filtrationthe reaction was filtered through Celite
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in DMF
  7. custompurified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

Sources & evidence

ORD record
ord-19fb71dd94a74ef994b0efa6f179b173
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

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