Sodium Carbonate → 3-(4-Amino-2-chlorothieno[3,2-d]pyrimidin-7-yl)benzoic acid
Reaction equation
Br[C:2]1[C:6]2[N:7]=[C:8]([Cl:12])[N:9]=[C:10]([NH2:11])[C:5]=2[S:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].B([C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[C:25]([OH:27])=[O:26])(O)O.CC(C1C=C(C(C)C)C(C2C(P(C(C)(C)C)C(C)(C)C)=CC=CC=2)=C(C(C)C)C=1)C>O1CCOCC1>[NH2:11][C:10]1[C:5]2[S:4][CH:3]=[C:2]([C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=3)[C:25]([OH:27])=[O:26])[C:6]=2[N:7]=[C:8]([Cl:12])[N:9]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
7-Bromo-2-chlorothieno[3,2-d]pyrimidin-4-amine (500 mg, 1.90 mmol) was dissolved in dioxane (10 mL) and 2.0 N sodium carbonate (2.85 mL, 5.70 mmol) and 3-boronobenzoic acid (316 mg, 1.90 mmol) were added. Nitrogen was flown to the mixture solution for 10 minutes and then Pd2(PPh3)Cl2 (80 mg, 0.11 mmol) and t-ButylXphos (73 mg, 0.17 mmol) were added. The reaction mixture solution was stirred at 90° C. for 6 hours and then filtered with celite. The organic layer was concentrated and then 2.0 N sodium hydroxide solution was added until the pH reached 10. After extracting with ethyl acetate, the aqueous layer was adjusted to pH 5 by adding 2.0 N hydrochloric acid solution. Thus prepared white solid was filtered and dried using nitrogen gas. The resultant target compound (380 mg, 65% yield) was used in the following reaction without purification.
Workup
- filtrationfiltered with celite
- concentrationThe organic layer was concentrated
- addition2.0 N sodium hydroxide solution was added until the pH
- extractionAfter extracting with ethyl acetate
- additionby adding 2.0 N hydrochloric acid solution
- filtrationThus prepared white solid was filtered
- customdried
Sources & evidence
- ORD record
- ord-ebf590a4d2e946ee85ac384003d0b8dc
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09422307B2
Reaction notes
Loading…