Potassium Carbonate → 5-[3'-Amino-6-ethoxy-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-ylmethyl]-pyrimidine-2,4-diamine

HRID 2416311Notes

Reaction equation

HRID 2416311 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([OH:26])=[CH:10][C:11]([CH2:17][C:18]3[C:19]([NH2:25])=[N:20][C:21]([NH2:24])=[N:22][CH:23]=3)=[CH:12][C:13]=2[O:14][CH2:15][CH3:16])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:38][C:39]([F:42])([F:41])[F:40])(=O)=O>C(#N)C>[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH2:15][CH3:16])=[CH:12][C:11]([CH2:17][C:18]3[C:19]([NH2:25])=[N:20][C:21]([NH2:24])=[N:22][CH:23]=3)=[CH:10][C:9]=2[O:26][CH2:38][C:39]([F:42])([F:41])[F:40])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 5565652,2,2-Trifluoroethyl Methanesulfonate2×HCID 226369793'-Amino-4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-biphenyl-2-ol

Product 1

HCID 226369015-[3'-Amino-6-ethoxy-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-ylmethyl]-pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

3′-Amino-4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-biphenyl-2-ol (527 mg; 1.5 mmol) is suspended in acetonitrile (60 ml; dried over a molecular sieve), potassium carbonate (621 mg; 4.5 mmol) is added and the mixture is heated to a bath temperature of 100° C. 2,2,2-Trifluoroethyl methanesulphonate (0.353 ml; 3.0 mmol) is added and the mixture is boiled under reflux for 3 hours. After this period of time, potassium carbonate (414 mg; 3 mmol) and 2,2,2-trifluoroethyl methanesulphonate (0.353 ml; 3.0 mmol) are again added and the mixture is stirred under reflux for a further 2 hours. The same procedure is repeated four more times at intervals of two hours. The suspension is then filtered with suction and the filtrate is concentrated. The residue is chromatographed over silica gel (120 g) with methylene chloride/methanol/NH4OH (1/1 mixture of 90/10/1 and 19/1/0.05).

Workup

  1. additionis added
  2. temperatureunder reflux for 3 hours
  3. temperatureunder reflux for a further 2 hours
  4. customat intervals of two hours
  5. filtrationThe suspension is then filtered with suction
  6. concentrationthe filtrate is concentrated
  7. customThe residue is chromatographed over silica gel (120 g) with methylene chloride/methanol/NH4OH (1/1 mixture of 90/10/1 and 19/1/0.05)

Sources & evidence

ORD record
ord-c12e582754a0450aaaf69a064ea15210
Source dataset
uspto-grants-2004_11
Patent number
US06821980B1

Reaction notes

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