Hydrochloric Acid → 5-Cyano-4-ethylamino-2-{4-[N-(2-hydroxy-3-piperidinopropyl)sulphamoyl]anilino}pyrimidine

HRID 1071939Notes

Reaction equation

HRID 1071939 reaction equation
[OH:1][CH:2]([CH2:15][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH2:3][NH:4][S:5]([C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1)(=[O:7])=[O:6].Cl.CC(O)CC.Cl[C:29]1[N:34]=[C:33]([NH:35][CH2:36][CH3:37])[C:32]([C:38]#[N:39])=[CH:31][N:30]=1>CO>[C:38]([C:32]1[C:33]([NH:35][CH2:36][CH3:37])=[N:34][C:29]([NH:12][C:11]2[CH:10]=[CH:9][C:8]([S:5](=[O:6])(=[O:7])[NH:4][CH2:3][CH:2]([OH:1])[CH2:15][N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:14][CH:13]=2)=[N:30][CH:31]=1)#[N:39]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6568(+-)-2-ButanolHCID 223905914-[N-(2-Hydroxy-3-piperidinopropyl)sulphamoyl]anilineHCID 223906122-Chloro-5-cyano-4-ethylaminopyrimidine

Product 1

HCID 223906225-Cyano-4-ethylamino-2-{4-[N-(2-hydroxy-3-piperidinopropyl)sulphamoyl]anilino}pyrimidineYield 10.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

4-[N-(2-Hydroxy-3-piperidinopropyl)sulphamoyl]aniline (Method 118; 200 mg, 0.64 mmol) was dissolved in methanol (4 ml). 1M Ethereal hydrogen chloride (1.28 ml, 1.28 mmol) was added and the mixture gently warmed to give a solution. The volatiles were partially evaporated to give a volume of approx. 1.5 ml. 2-Butanol (5 ml) was added and the cloudy solution warmed to 50° C. 2-Chloro-5-cyano-4-ethylaminopyrimidine (Method 56; 233 mg, 1.28 mmol) was added in portions and the reaction was then heated at 95° C. for 20 hours. The hot supernatant was decanted from the solid residue and the solution allowed to cool. The resulting precipitate was collected by filtration, washed with diethyl ether and suspended in water (approx. 35 ml). The suspension was adjusted to pH>10 with 2M aqueous sodium hydroxide solution and extracted with ethyl acetate (3×15 ml). The extracts were dried, the volatiles evaporated and the residue purified by chromatography on silica eluting with DCM/methanolic ammonia (100:0) increasing in polarity to (85:15). The product was triturated with diethyl ether and collected by filtration to give the title compound (30 mg, 10%). NMR: 1.15 (t, 3H), 1.35 (m, 2H), 1.43 (m, 4H), 2.10-2.35 (m, 6H), 2.68 (m, 1H), 2.83 (m, 1H), 3.48 (quin, 2H), 3.56 (m, 1H), 4.59 (s, 1H) 7.36 (brt, 1H), 7.70 (d, 2H), 7.88 (t, 1H), 7.95 (d, 2H), 8.40 (s, 1H) 10.16 (s, 1H); m/z: 460.

Workup

  1. temperaturethe mixture gently warmed
  2. customto give a solution
  3. customThe volatiles were partially evaporated
  4. customto give a volume of approx. 1.5 ml
  5. temperaturethe reaction was then heated at 95° C. for 20 hours
  6. customThe hot supernatant was decanted from the solid residue
  7. temperatureto cool
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed with diethyl ether
  10. extractionextracted with ethyl acetate (3×15 ml)
  11. customThe extracts were dried
  12. customthe volatiles evaporated
  13. customthe residue purified by chromatography on silica eluting with DCM/methanolic ammonia (100:0)
  14. temperatureincreasing in polarity to (85:15)
  15. customThe product was triturated with diethyl ether
  16. filtrationcollected by filtration

Sources & evidence

ORD record
ord-b7aa3a14804f4d62a92c4bb4a2aeac07
Source dataset
uspto-grants-2005_06
Patent number
US06908920B2

Reaction notes

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