3-Fluoro-4-(4-pyridinylsulfanyl)aniline → 6-ethyl-N4-[3-fluoro-4-(4-pyridinylsulfanyl)phenyl]-2,4-pyrimidinediamine

HRID 496018Notes

Reaction equation

HRID 496018 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH2:9][CH3:10])[N:3]=1.[F:11][C:12]1[CH:13]=[C:14]([CH:16]=[CH:17][C:18]=1[S:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)[NH2:15]>Cl>[CH2:9]([C:4]1[N:3]=[C:2]([NH2:1])[N:7]=[C:6]([NH:15][C:14]2[CH:16]=[CH:17][C:18]([S:19][C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[C:12]([F:11])[CH:13]=2)[CH:5]=1)[CH3:10]

Participants

4

Reactant 2

HCID 70592743-Fluoro-4-(4-pyridinylsulfanyl)anilineHCID 223243042-Amino-4-chloro-6-ethylpyrimidine2×

Product 1

HCID 223243146-ethyl-N4-[3-fluoro-4-(4-pyridinylsulfanyl)phenyl]-2,4-pyrimidinediamineYield 34%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

2-Amino-4-chloro-6-ethylpyrimidine (Intermediate A8, 55.1 mg, 0.25 mmol) and Intermediate B7(39.4 mg, 0.25 mmol) were suspended in 0.01 M aqueous HCl (500 μL). The mixture was refluxed for 6 h. The reaction was cooled to room temperature and the solvent was evaporated by vacuum. The residue was purified by reversed phase chromatography on a YMC Pack-pro C18 column (trademark) eluting with acetonitrile/H2O (10:90-90:10 gradient). The compound was further purified by preparative TLC eluting with CH2Cl2-MeOH (90:10). Desired compound (2.9 mg, 0.0085 mmol; 34% yield); 1H NMR (Methanol-d4) 8.16 (dd, J=1.7, 4.7, 2H), 8.00-8.04 (m, 1H), 7.37 (m, 2H), 6.93 (dd, J=1.8, 4.9, 2H), 5.91 (s, 1H), 2.39 (q, J=7.7, 2H), 1.13 (t, J=7.5, 3H); ES MS [M+H]+=342; TLC (CH2Cl2-MeOH, 90:10); Rf=0.48.

Workup

  1. temperatureThe mixture was refluxed for 6 h
  2. customthe solvent was evaporated by vacuum
  3. customThe residue was purified by reversed phase chromatography on a YMC Pack-pro C18 column (trademark)
  4. washeluting with acetonitrile/H2O (10:90-90:10 gradient)
  5. customThe compound was further purified by preparative TLC
  6. washeluting with CH2Cl2-MeOH (90:10)

Sources & evidence

ORD record
ord-7833ac07c30b48ea9a35b1716313c3f4
Source dataset
uspto-grants-2005_09
Patent number
US06943172B2

Reaction notes

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