Sodium Carbonate → N-(4-(4-(5-methylthiazol-2-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide

HRID 499055Notes

Reaction equation

HRID 499055 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]([CH:19]3[CH2:21][CH2:20]3)=[O:18])=[CH:12][CH:11]=2)[N:3]=1.[NH2:22][C:23]1[S:24][C:25]([CH3:28])=[CH:26][N:27]=1.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.C(=O)([O-])[O-].[Na+].[Na+]>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]>[CH3:28][C:25]1[S:24][C:23]([NH:22][C:2]2[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][C:10]3[CH:15]=[CH:14][C:13]([NH:16][C:17]([CH:19]4[CH2:21][CH2:20]4)=[O:18])=[CH:12][CH:11]=3)[N:3]=2)=[N:27][CH:26]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 3517702-Amino-5-methylthiazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 46864056N-(4-((4,6-Dichloropyrimidin-2-yl)thio)phenyl)cyclopropanecarboxamide

Product 1

HCID 59420771N-(4-(4-(5-methylthiazol-2-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)cyclopropanecarboxamideYield 70.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A suspension of N-(4-(4,6-dichloropyrimidin-2-ylthio)phenyl)cyclopropane-carboxamide (5.0 g, 14.7 mmol), amino-5-methylthiazole (1.85 g, 16.2 mmol), tris(dibenzylideneacetone)dipalladium (0.673 g, 0.74 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-xanthene (0.636 g, 1.10 mmol) and sodium carbonate (2.18 g, 20.58 mmol) in dioxane (120 ml) was heated at 100° C. for 2 h. The reaction mixture was then allowed to cool to room temperature before the tan precipitate was collected by filtration, washed with ethyl acetate (50 ml) water (3×30 ml) and then diethyl ether (50 ml) and dried to give title compound as a tan solid (4.32 g, 70%). 1H NMR (DMSO) 0.81 (4H, d), 1.83 (1H, m), 2.09 (3H, s), 6.35 (1H, br s), 6.88 (1H, s), 7.53 (2H, d), 7.74 (2H, d), 10.48 (1H, s). MS(ES+): 418.

Workup

  1. temperatureto cool to room temperature before the tan precipitate
  2. filtrationwas collected by filtration
  3. washwashed with ethyl acetate (50 ml) water (3×30 ml)
  4. dry with materialdiethyl ether (50 ml) and dried

Sources & evidence

ORD record
ord-19727b64ee7d432cbe9e3f4541f88519
Source dataset
uspto-grants-2010_08
Patent number
US07767672B2

Reaction notes

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