3-Methoxypropylamine → 2-{4-[N-(3-Methoxypropyl)sulphamoyl]anilino}-4-(1-methylimidazol-5-yl)pyrimidine

HRID 1064310Notes

Reaction equation

HRID 1064310 reaction equation
Cl[S:2]([OH:5])(=O)=[O:3].[NH:6]([C:13]1[N:18]=[C:17]([C:19]2[N:23]([CH3:24])[CH:22]=[N:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(C(C)C)CC)(C)C.[CH3:34][O:35][CH2:36][CH2:37][CH2:38][NH2:39]>S(Cl)(Cl)=O.CCOC(C)=O>[CH3:34][O:35][CH2:36][CH2:37][CH2:38][NH:39][S:2]([C:10]1[CH:11]=[CH:12][C:7]([NH:6][C:13]2[N:18]=[C:17]([C:19]3[N:23]([CH3:24])[CH:22]=[N:21][CH:20]=3)[CH:16]=[CH:15][N:14]=2)=[CH:8][CH:9]=1)(=[O:5])=[O:3]

Participants

7

Reactant 4

HCID 16723-MethoxypropylamineHCID 24638Chlorosulfonic acidHCID 81531DiisopropylethylamineHCID 222734872-Anilino-4-(1-methylimidazol-5-yl)pyrimidine

Product 1

HCID 222734712-{4-[N-(3-Methoxypropyl)sulphamoyl]anilino}-4-(1-methylimidazol-5-yl)pyrimidineYield 28%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

Chlorosulphonic acid (0.22 ml, 3.18 mmol) was added to suspension of 2-anilino-4-(1-methylimidazol-5-yl)pyrimidine (Example 14; 200 mg, 0.80 mmol) in thionyl chloride (4 ml) cooled at 0° C. The mixture was allowed to warm to ambient temperature, stirred for 15 minutes then heated at reflux for 20 minutes. The volatiles were removed by evaporation and the solid residue dried under high vacuum. The residue was suspended in pyridine (3 ml), cooled to −20° C. and diisopropylethyl amine (0.56 ml, 3.98 mmol) followed by 3-methoxypropyl amine (0.16 ml, 1.60 mmol) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 30 minutes. EtOAc (15 ml) was added and the mixture washed with saturated aqueous sodium hydrogen carbonate solution (15 ml) and then brine (15 ml). The solvent was removed by evaporation and the residue purified by column chromatography eluting with DCM and 2M methanolic ammonia solution (100:0 increasing in polarity to 85:15) to give the title compound 89 mg, (28%) as a solid product. NMR: 1.75 (m, 2H), 2.76 (q, 2H), 3.14 (s, 3H), 3.22-3.30 (m, 2H), 4.01 (s, 3H), 7.25 (d, 1H), 7.34 (t, 1H), 7.70 (d, 2H), 7.77 (s, 1H), 7.83 (s, 1H), 7.91 (d, 2H), 8.47 (d, 1H), 9.92 (s, 1H); m/z 4.03.

Workup

  1. temperatureto warm to ambient temperature
  2. temperaturethen heated
  3. temperatureat reflux for 20 minutes
  4. customThe volatiles were removed by evaporation
  5. customthe solid residue dried under high vacuum
  6. temperaturecooled to −20° C.
  7. additionwas added
  8. temperatureto warm to ambient temperature
  9. stirringstirred for 30 minutes
  10. washthe mixture washed with saturated aqueous sodium hydrogen carbonate solution (15 ml)
  11. customThe solvent was removed by evaporation
  12. customthe residue purified by column chromatography
  13. washeluting with DCM and 2M methanolic ammonia solution (100:0 increasing in polarity to 85:15)

Sources & evidence

ORD record
ord-400fa12edcd74554a41edca714ca05cf
Source dataset
uspto-grants-2005_11
Patent number
US06969714B2

Reaction notes

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