Water → 6-Chloro-2-[1-(1-isoquinolyl)ethylsulfanyl]pyrimidin-4-amine

HRID 1637756Notes

Reaction equation

HRID 1637756 reaction equation
S(O)(=O)(=O)C.[NH2:6][C:7]1[CH:12]=[C:11]([Cl:13])[N:10]=[C:9]([SH:14])[N:8]=1.[H-].[Na+].Cl[CH:18]([C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][N:21]=1)[CH3:19].O>CN(C)C=O>[NH2:6][C:7]1[CH:12]=[C:11]([Cl:13])[N:10]=[C:9]([S:14][CH:18]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=[CH:22][N:21]=2)[CH3:19])[N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 187999761-(1-Chloroethyl)-isoquinolineHCID 178505342HCID 178505342, compound

Product 1

HCID 4927556-Chloro-2-[1-(1-isoquinolyl)ethylsulfanyl]pyrimidin-4-amineYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-Amino-6-chloro-2-mercapto-pyrimidine mesylate salt (1.29 g, 5 mmole) is dissolved in 8 ml dry dimethylformamide in a 50 ml one neck round bottom flask under nitrogen. The solution is treated with 60% sodium hydride (400 mg, 10 mmole) (exotherm) and the mixture is stirred 45 min. 1-(1-chloroethyl)-isoquinoline (958 mg, 5 mmole) in 2×2 ml dry dimethylformamide, is added to the reaction and the mixture is stirred overnight at room temperature. The reaction mixture is poured into 200 ml water and is extracted with 4×50 ml ethyl acetate. The combined organics are backwashed with 4×50 ml 50% saturated sodium chloride. The organics are dried over potassium carbonate and are concentrated in vacuo to a yellow oil. The crude material is chromatographed over 100 g silica gel (230-400 mesh), eluting with 25% acetone/hexane while collecting 22 ml fractions. Fractions 27-39 are combined and concentrated to given a pale yellow foam. Crystallization from diethyl ether afforded 847 mg (54%) of 4-Amino-6-chloro-2-(1-(1-isoquinolyl)ethyl)thio-pyrimidine (Cpd #232) as an off-white solid.

Workup

  1. stirringthe mixture is stirred overnight at room temperature
  2. extractionis extracted with 4×50 ml ethyl acetate
  3. dry with materialThe organics are dried over potassium carbonate
  4. concentrationare concentrated in vacuo to a yellow oil
  5. customThe crude material is chromatographed over 100 g silica gel (230-400 mesh)
  6. washeluting with 25% acetone/hexane
  7. customwhile collecting 22 ml fractions
  8. concentrationconcentrated
  9. customCrystallization from diethyl ether

Sources & evidence

ORD record
ord-439a271c7b7a47a8aaaa5735c7702120
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

Loading…