5-(3-Ethoxy-5-hydroxy-4-iodo-benzyl)-pyrimidine-2,4-diamine → Tetrahydropyran-4-sulphonic acid 3'-amino-4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-biphenyl-2-yl ester

HRID 2416336Notes

Reaction equation

HRID 2416336 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:16]=[C:17]([OH:20])[C:18]=1I)[CH2:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1)[CH3:2].C[C:22]([O-])([CH3:24])[CH3:23].[K+].[O:27]1[CH2:32][CH2:31][CH:30]([S:33](Cl)(=[O:35])=[O:34])[CH2:29][CH2:28]1>O1CCCC1>[NH2:10][C:9]1[CH:8]=[C:7]([C:18]2[C:4]([O:3][CH2:1][CH3:2])=[CH:5][C:6]([CH2:7][C:8]3[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=3)=[CH:16][C:17]=2[O:20][S:33]([CH:30]2[CH2:31][CH2:32][O:27][CH2:28][CH2:29]2)(=[O:35])=[O:34])[CH:24]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 226368575-(3-Ethoxy-5-hydroxy-4-iodo-benzyl)-pyrimidine-2,4-diamineHCID 22637030Oxane-4-sulfonyl chlorideHCID 23665647Potassium tert-butoxide

Product 1

HCID 17937307Tetrahydropyran-4-sulphonic acid 3'-amino-4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-biphenyl-2-yl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

5-(3-Ethoxy-5-hydroxy-4-iodo-benzyl)-pyrimidine-2,4-diamine (see example 32 stage a) (2,300 mg; 5.96 mmol) is dissolved in tetrahydrofuran (70 ml), potassium tert-butylate (1,000 mg; 8.9 mmol) is added and the mixture is cooled to −20° C. Tetrahydropyran-4-sulphonyl chloride (2.2 g; 11.9 mmol) is added at this temperature and the mixture is then stirred for one hour at −20° C. The reaction mixture is poured on to ice-water and extracted twice with ethyl acetate. The organic phase is dried over sodium sulphate, the salts are filtered off and the solvent is evaporated off. The residue is chromatographed over silica gel with methylene chloride 1 methanol (19/1) and 0.5% ammonia. The pure fractions are co mbidand the solvent is evaporated off.

Workup

  1. extractionextracted twice with ethyl acetate
  2. dry with materialThe organic phase is dried over sodium sulphate
  3. filtrationthe salts are filtered off
  4. customthe solvent is evaporated off
  5. customThe residue is chromatographed over silica gel with methylene chloride 1 methanol (19/1) and 0.5% ammonia
  6. customis evaporated off

Sources & evidence

ORD record
ord-487373f4f06d43f7a7cb0325d46b09e3
Source dataset
uspto-grants-2004_11
Patent number
US06821980B1

Reaction notes

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