Sodium Carbonate → HCID 68110407, compound

HRID 525090Notes

Reaction equation

HRID 525090 reaction equation
Br[C:2]1[C:10]2[C:9]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[N:8][CH:7]=[N:6][C:5]=2[S:4][C:3]=1[CH3:21].[O:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH:24]=[C:23]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[O:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH:24]=[C:23]1[C:2]1[C:10]2[C:9]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[N:8][CH:7]=[N:6][C:5]=2[S:4][C:3]=1[CH3:21]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2776266Benzo[b]furan-2-boronic acidHCID 68110526HCID 68110526, compound

Product 1

HCID 68110407HCID 68110407, compoundYield 36.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-N-[5-bromo-6-methylthieno[2,3-d]pyrimidin-4-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine (300 mg, 0.81 mmol, 1.00 equiv) in anhydrous toluene (6 mL) was added (1-benzofuran-2-yl)boronic acid (292 mg, 1.80 mmol, 2.30 equiv), sodium carbonate (286 mg, 2.70 mmol, 3.40 equiv), PPh3 (79 mg, 0.30 mmol, 0.35 equiv), Pd(OAc)2 (22 mg, 0.10 mmol, 0.12 equiv) and water (2 mL) at room temperature under nitrogen. The resulting mixture was stirred for 6 h at 100° C. in an oil bath. After cooled to room temperature, the reaction was then quenched water and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (8:1) to give the desired 4-N-[5-(1-benzofuran-2-yl)-6-methylthieno[2,3-d]pyrimidin-4-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine (120 mg, 36%) as a off-white solid. MS (ES, m/z): 407 [M+H+]. 1H NMR (300 MHz, CDCl3) δ 8.46 (s, 1H), 7.71 (d, 1H), 7.57 (m, 2H), 6.86 (s, 1H), 5.62 (d, 1H), 4.00 (m, 1H), 2.59 (s, 3H), 2.33 (s, 6H), 2.13 (m, 3H), 1.94 (m, 2H), 1.44 (dd, 2H), 0.98 (dd, 2H).

Workup

  1. temperatureAfter cooled to room temperature
  2. extractionquenched water and extracted with 3×50 mL of ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-0921be71f7364e5e8ad79f69cbf4bc01
Source dataset
uspto-grants-2016_05
Patent number
US09340554B2

Reaction notes

Loading…