Hydrochloric Acid → HCID 24887749, compound

HRID 2375268Notes

Reaction equation

HRID 2375268 reaction equation
Cl[S:2]([OH:5])(=O)=[O:3].[NH:6]([C:13]1[N:18]=[C:17]([C:19]2[N:23]([CH2:24][CH3:25])[C:22]([CH3:26])=[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.[CH2:27]([O:29][CH2:30][CH2:31][NH2:32])[CH3:28].C(N(CC)C)C.Cl.CCOCC>S(Cl)(Cl)=O.CO>[CH2:24]([N:23]1[C:19]([C:17]2[CH:16]=[CH:15][N:14]=[C:13]([NH:6][C:7]3[CH:12]=[CH:11][C:10]([S:2](=[O:5])(=[O:3])[NH:32][CH2:31][CH2:30][O:29][CH2:27][CH3:28])=[CH:9][CH:8]=3)[N:18]=2)=[CH:20][N:21]=[C:22]1[CH3:26])[CH3:25]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 12022DiethylmethylamineHCID 24638Chlorosulfonic acidHCID 66970EthoxyethylamineHCID 22273557HCID 22273557, compound

Product 1

HCID 24887749HCID 24887749, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

Chlorosulphonic acid (280 μl, 4 mmol) was added dropwise to solution of 2-anilino-4-(1-ethyl-2-methylimidazol-5-yl)pyrimidine (Method 30; 279 mg, 1 mmol) in thionyl chloride (5 ml) cooled at 0° C. and the mixture stirred at 0° C. for 10 minutes then heated at 90° C. for 90 minutes. The volatiles were removed by evaporation and the residue was dried under high vacuum (<2 mmHg) for 1 hour. The resulting solid was placed under nitrogen and a solution of 2-ethoxyethylamine (356 mg, 4 mmol) and diethylmethylamine (1 ml, 15 mmol) in MeOH (3 ml) added. The mixture was stirred for 15 minutes and the volatiles were evaporated in vacuo. Water (20 ml) was added and extracted DCM (2×25 ml). DCM was dried and evaporated in vacuo. The residue was purified by flash chromatography on silica gel eluting with DCM:MeOH (100:0 increasing in polarity to 97:3) to yield a white foam. The white foam was dissolved in MeOH (3 ml) and treated with 1M HCl in ether (0.55 ml, 0.55 mmol). The solvent was evaporated in vacuo and the resultant solid triturated with ether, collected by filtration and dried-under vacuum at 60° C. to yield the title compound (128 mg, 47%) as a yellow solid. NMR: 1.05 (t, 3H), 1.30 (t, 3H), 2.76 (s, 3H), 2.88 (m, 2H), 3.32 (m, 4H), 4.76 (m, 2H), 7.37 (d, 1H), 7.52 (m, 1H), 7.73 (d, 2H), 7.90 (d, 2H), 8.43 (s, 1H), 8.65 (d, 1H), 10.14 (brs, 1H); m/z 431.

Workup

  1. temperaturethen heated at 90° C. for 90 minutes
  2. customThe volatiles were removed by evaporation
  3. customthe residue was dried under high vacuum (<2 mmHg) for 1 hour
  4. stirringThe mixture was stirred for 15 minutes
  5. customthe volatiles were evaporated in vacuo
  6. additionWater (20 ml) was added
  7. extractionextracted DCM (2×25 ml)
  8. dry with materialDCM was dried
  9. customevaporated in vacuo
  10. customThe residue was purified by flash chromatography on silica gel eluting with DCM:MeOH (100:0 increasing in polarity to 97:3)
  11. customto yield a white foam
  12. customThe solvent was evaporated in vacuo
  13. customthe resultant solid triturated with ether
  14. filtrationcollected by filtration and dried-under vacuum at 60° C.

Sources & evidence

ORD record
ord-3dfcdb853d2f42eeb2f159ab9b13dee2
Source dataset
uspto-grants-2008_12
Patent number
US07465728B2

Reaction notes

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