Sodium Carbonate → HCID 121268926, compound

HRID 2199634Notes

Reaction equation

HRID 2199634 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=4)=[O:19])=[CH:13][C:11]=3[CH:12]=2)=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Cl[C:42]1[N:47]=[CH:46][CH:45]=[CH:44][N:43]=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[NH2:1][C:2]1[C:7]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([C:28]([F:29])([F:31])[F:30])[CH:22]=4)=[O:19])=[CH:13][C:11]=3[CH:12]=2)=[CH:6][C:5]([C:42]2[N:47]=[CH:46][CH:45]=[CH:44][N:43]=2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 744042-ChloropyrimidineHCID 131735702HCID 131735702, compound

Product 1

HCID 121268926HCID 121268926, compoundYield 18.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

1-{2-[2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-1-benzothien-5-yl}-3-[4-chloro-3-(trifluoromethyl)phenyl]urea (194 mg, 0.33 mmoles) and 2-chloropyrimidine (38 mg, 0.3 mmoles) was added to a mixture of 6 ml of dioxane and 2 ml of 2M aqueous Sodium Carbonate. Next, Palladium(II) Acetate (10 mol %, 7 mg) and Triphenylphosphene (20 mol %, 16 mg) was added, followed by 2 ml of dioxane. Dry nitrogen was bubbled through the resulting solution for 15 minutes. Following this, the reaction mixture was set up with a reflux condenser, under nitrogen atmosphere, and heated at 95 C overnight. The reaction was then cooled to room temperature and 40 ml of ethyl acetate was added. The mixture was transferred to a separatory funnel and extracted with saturated Sodium Bicarbonate (3×40 ml) followed by saturated NaCl (3×40 ml). The organic layer was dried with anhydrous Sodium Sulfate, loaded onto silica and columned using ethyl acetate/hexanes, to give 30 mg of the product. 1H NMR (<dmso>) δ: 9.19 (s, 1H), 9.02 (d, J=2.1 Hz, 1H), 8.99 (s, 1H), 8.83 (d, J=4.7 Hz, 2H), 8.47 (d, J=2.1 Hz, 1H), 8.14 (dd, J=13.8, 2.1 Hz, 2H), 7.90 (d, J=8.8 Hz, 1H), 7.68 (s, 1H), 7.58-7.66 (m, 2H), 7.41 (dd, J=8.8, 2.1 Hz, 1H), 7.35 (t, J=4.8 Hz, 1H), 6.71 (s, 2H).

Workup

  1. customDry nitrogen was bubbled through the resulting solution for 15 minutes
  2. customwas set up with a reflux condenser, under nitrogen atmosphere
  3. temperatureheated at 95 C overnight
  4. addition40 ml of ethyl acetate was added
  5. customThe mixture was transferred to a separatory funnel
  6. extractionextracted with saturated Sodium Bicarbonate (3×40 ml)
  7. dry with materialThe organic layer was dried with anhydrous Sodium Sulfate

Sources & evidence

ORD record
ord-d0feac435cb241a0bf87c3e8bbbcbb38
Source dataset
uspto-grants-2016_06
Patent number
US09359336B2

Reaction notes

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