Sodium Bicarbonate → 2-Amino-4-(4-benzyloxy-2-methyl-phenyl)-thieno[2,3-d]pyrimidine-6-carboxylic acid ethyl ester

HRID 237377Notes

Reaction equation

HRID 237377 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1B(O)O.[CH2:19]([O:21][C:22]([C:24]1[S:34][C:27]2[N:28]=[C:29]([NH2:33])[N:30]=[C:31](Cl)[C:26]=2[CH:25]=1)=[O:23])[CH3:20].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:19]([O:21][C:22]([C:24]1[S:34][C:27]2[N:28]=[C:29]([NH2:33])[N:30]=[C:31]([C:3]3[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)=[CH:7][C:2]=3[CH3:1])[C:26]=2[CH:25]=1)=[O:23])[CH3:20]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27732454-Benzyloxy-2-methylphenylboronic acidHCID 16096301Ethyl 2-amino-4-chlorothieno(2,3-d)pyrimidine-6-carboxylate

Product 1

HCID 112009432-Amino-4-(4-benzyloxy-2-methyl-phenyl)-thieno[2,3-d]pyrimidine-6-carboxylic acid ethyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2-methyl-4-benzyloxyphenylboronic acid (225 mg; 0.93 mmol) was added to 2-Amino-4-chloro-thieno[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (example 1; step 1) (200 mg; 0.776 mmol) in DMF (10 mL). NaHCO3 (1.0M aq. Solution; 2.33 mL) was added and mixture degassed with N2. Pd(PPh3)2Cl2 was added and reaction mixture heated at 80 degrees C. for 5 hours Reaction mixture was allowed to cool to room temperature and DMF removed in vacuo. The residue was partitioned between ethyl acetate (50 mL) and sat. NaCl (aq) (50 mL) Organic phase was dried over Na2SO4 and filtered, filtrate solvents removed in vacuo to afford a yellow oil which was purified by ion-exchange chromatography (IST SCX-2 column) to afford product as a brown-yellow solid (230 mg; 71%)

Workup

  1. custommixture degassed with N2
  2. additionPd(PPh3)2Cl2 was added
  3. customreaction mixture
  4. customfor 5 hours Reaction mixture
  5. temperatureto cool to room temperature
  6. customDMF removed in vacuo
  7. customThe residue was partitioned between ethyl acetate (50 mL) and sat. NaCl (aq) (50 mL) Organic phase
  8. dry with materialwas dried over Na2SO4
  9. filtrationfiltered
  10. customfiltrate solvents removed in vacuo
  11. customto afford a yellow oil which
  12. customwas purified by ion-exchange chromatography (IST SCX-2 column)

Sources & evidence

ORD record
ord-f0038655cb0b47d6b8750bce6f06f939
Source dataset
uspto-grants-2014_02
Patent number
US08642594B2

Reaction notes

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