2-Aminothiazole → 2,6-dichloro-N-(2-(thiazol-2-ylamino)pyridin-4-yl)benzamide

HRID 449864

Reaction equation

HRID 449864 reaction equation
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[S:21][CH:22]=[CH:23][N:24]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]2[S:21][CH:22]=[CH:23][N:24]=2)[CH:7]=1)=[O:18]

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 75464886N-(2-Bromopyridin-4-yl)-2,6-dichlorobenzamide

Product 1

HCID 596182462,6-dichloro-N-(2-(thiazol-2-ylamino)pyridin-4-yl)benzamideYield 25.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A 25 mL microwave tube containing N-(2-bromopyridin-4-yl)-2,6-dichlorobenzamide (0.21 g, 0.61 mmol), 2-aminothiazole (92 mg, 0.92 mmol), Pd2(dba)3 (56 mg, 0.061 mmol), Cs2CO3 (0.4 g, 1.22 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 71 mg, 0.122 mmol), and dioxane (8 mL) was degassed and then charged with N2 (3×). The resulting mixture was heated at 80° C. overnight. After cooling, the mixture was diluted with dioxane (20 mL) and filtered through celite. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase HPLC (Gemini, 200 mm×25 mm, gradient: CH3CN/0.05% NH3.H2O, 50-80, 10 min) to afford the desired product (56.4 mg, yield: 25%). 1HNMR: (DMSO-d6, 400 MHz): 611.26 (s, 1H), 11.13 (s, 1H), 8.21 (d, J=6.0 Hz, 1H), 7.61-7.50 (m, 4H), 7.36 (d, J=3.6 Hz, 1H), 7.11 (q, J=1.6, 6.0 Hz, 1H), 6.98 (d, J=3.6 Hz, 1H). LCMS (ESI) m/z: 364.8 [M+H+]

Workup

  1. customwas degassed
  2. additioncharged with N2 (3×)
  3. temperatureAfter cooling
  4. additionthe mixture was diluted with dioxane (20 mL)
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by reverse-phase HPLC (Gemini, 200 mm×25 mm, gradient: CH3CN/0.05% NH3.H2O, 50-80, 10 min)

Sources & evidence

ORD record
ord-3118848d6bdc46cebe46f27181f6a3d1
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Linked notes

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