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Potassium Carbonate → 2-chloro-N-(3,4,5-trimethoxyphenyl)thieno[3,2-d]pyrimidin-7-amine

HRID 2042236
Notes
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Reaction equation

HRID 2042236 reaction equation
Br[C:2]1[C:6]2[N:7]=[C:8]([Cl:11])[N:9]=[CH:10][C:5]=2[S:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:18][O:19][C:20]1[CH:21]=[C:22]([NH2:30])[CH:23]=[C:24]([O:28][CH3:29])[C:25]=1[O:26][CH3:27].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>CC(O)CC.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]>[Cl:11][C:8]1[N:9]=[CH:10][C:5]2[S:4][CH:3]=[C:2]([NH:30][C:22]3[CH:23]=[C:24]([O:28][CH3:29])[C:25]([O:26][CH3:27])=[C:20]([O:19][CH3:18])[CH:21]=3)[C:6]=2[N:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 322853,4,5-TrimethoxyanilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 569657247-Bromo-2-chlorothieno(3,2-d)pyrimidine

Product 1

HCID 866732242-chloro-N-(3,4,5-trimethoxyphenyl)thieno[3,2-d]pyrimidin-7-amineYield 43%

Reagents, catalysts & solvents

2
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6568(+-)-2-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

7-Bromo-2-chlorothieno[3,2-d]pyrimidine (200 mg, 0.81 mmol) was dissolved in 2-butanol (4 mL) and then potassium carbonate (223 mg, 1.61 mmol) and 3,4,5-trimethoxybenzenamine (110 mg, 0.81 mmol) were added. After blowing nitrogen to the reaction mixture for 10 minutes, Pd2(dba)3 (50 mg, 0.048 mmol) and Xphos (35 mg, 0.073 mmol) were added. The reaction mixture was stirred at 80° C. for 2.5 hours and then filtered with celite. The filtrate was diluted with ethyl acetate and washed with brine. The organic layer was dried with magnesium sulfate, filtered with celite, and then concentrated. Purification by chromatography (15% ethyl acetate/hexane) yielded the target compound (120 mg, 43% yield).

Workup

  1. customfor 10 minutes
  2. filtrationfiltered with celite
  3. additionThe filtrate was diluted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered with celite
  7. concentrationconcentrated
  8. customPurification by chromatography (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7a752c1ca70b483eb182cc65ae1a475b
Source dataset
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08586580B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes