Hydrochloric Acid → 4-(1-Isopropyl-2-methylimidazol-5-yl)-2-{4-[N-(2-ethoxyethyl)sulphamoyl]anilino}pyrimidine

HRID 2375271Notes

Reaction equation

HRID 2375271 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH:13]([CH3:15])[CH3:14])[C:11]([CH3:16])=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[CH2:17]([O:19][CH2:20][CH2:21][NH:22][S:23]([C:26]1[CH:31]=[CH:30][C:29](I)=[CH:28][CH:27]=1)(=[O:25])=[O:24])[CH3:18].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].Cl.CCOCC>O1CCOCC1.CO.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH:13]([N:12]1[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:29]3[CH:28]=[CH:27][C:26]([S:23](=[O:24])(=[O:25])[NH:22][CH2:21][CH2:20][O:19][CH2:17][CH3:18])=[CH:31][CH:30]=3)[N:7]=2)=[CH:9][N:10]=[C:11]1[CH3:16])([CH3:14])[CH3:15]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 634876Binap, (A+-)-HCID 3870475N-(2-ethoxyethyl)-4-iodobenzenesulphonamideHCID 23676156Sodium t-butoxideHCID 25178483HCID 25178483, compound

Product 1

HCID 248879504-(1-Isopropyl-2-methylimidazol-5-yl)-2-{4-[N-(2-ethoxyethyl)sulphamoyl]anilino}pyrimidine

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 887MethanolSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 2-amino-4-(1-isopropyl-2-methylimidazol-5-yl)pyrimidine (Method 39; 163 mg, 0.75 mmol), N-(2-ethoxyethyl)-4-iodobenzenesulphonamide (Method 44; 400 mg, 1.13 mmol), tris(dibenzylideneacetone) dipalladium (0) (35 mg, 0.038 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (47 mg, 0.076 mmol) in dioxane (10 ml) was added sodium t-butoxide (258 mg, 2.69 mmol) and the mixture heated at 80° C. overnight. The reaction was cooled to room temperature and MeOH 105 ml) was added and the mixture poured onto an Isolute SCX-2 column, eluted first with MeOH (10×30 ml) and the product was then eluted with 5% methanolic ammonia (10×30 ml). The solvent was removed by evaporation and the residue purified by flash chromatography on silica gel eluting with DCM/MeOH (100:0 increasing in polarity to 97:3) to yield a foam which was dissolved in MeOH (2 ml) and treated with 1N HCl in ether (350 μl, 0.35 mmol) for 5 minutes. Solvent was evaporated in vacuo to yield a yellow foam which was triturated with ether to yield after filtration the title compound as a yellow solid (141 mg, 39%) NMR: 1.05 (t, 3H), 1.53 (d, 6H), 2.80 (s, 3H), 2.85 (q, 2H), 3.32 (m, 4H), 5.58 (m, 1H),7.21 (d, 1H), 7.52 (t, 1H), 7.73 (d, 2H), 7.86 (d, 2H), 8.39 (s, 1H), 8.68 (d, 1H), 10.18 (brs, 1H); m/z 445.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. additionthe mixture poured onto an Isolute SCX-2 column
  3. washeluted first with MeOH (10×30 ml)
  4. washthe product was then eluted with 5% methanolic ammonia (10×30 ml)
  5. customThe solvent was removed by evaporation
  6. customthe residue purified by flash chromatography on silica gel eluting with DCM/MeOH (100:0 increasing in polarity to 97:3)
  7. customto yield a foam which
  8. customSolvent was evaporated in vacuo
  9. customto yield a yellow foam which
  10. customwas triturated with ether
  11. customto yield
  12. filtrationafter filtration the title compound as a yellow solid (141 mg, 39%) NMR: 1.05 (t, 3H), 1.53 (d, 6H), 2.80 (s, 3H), 2.85 (q, 2H), 3.32 (m, 4H), 5.58 (m, 1H),7.21 (d, 1H), 7.52 (t, 1H), 7.73 (d, 2H), 7.86 (d, 2H), 8.39 (s, 1H), 8.68 (d, 1H), 10.18 (brs, 1H)

Sources & evidence

ORD record
ord-dc19a93e847544129731cf2756e91cdc
Source dataset
uspto-grants-2008_12
Patent number
US07465728B2

Reaction notes

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