Water → 6-Chloro-2-[1-(3-isoquinolyl)ethylsulfanyl]pyrimidin-4-amine

HRID 1637752Notes

Reaction equation

HRID 1637752 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[N:21]=[CH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2)[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[N:21]=[CH:22][C:23]3[C:28]([CH:29]=2)=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH3:19])[N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 187998313-(1-Chloroethyl)-isoquinolineHCID 178505342HCID 178505342, compound

Product 1

HCID 4927536-Chloro-2-[1-(3-isoquinolyl)ethylsulfanyl]pyrimidin-4-amineYield 57.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-Amino-6-chloro-2-mercapto-pyrimidine mesylate salt (1.79 g, 6.94 mmole) is dissolved in 12 ml dry dimethylformamide in a 50 ml one neck round bottom flask under nitrogen. The solution is treated with 60% sodium hydride (605 mg, 15.1 mmole) (exotherm) and the mixture is stirred one hour. 3-(1-chloroethyl)-isoquinoline (1.33 g, 6.94 mmole) in 2×3 ml dry dimethylformamide, is added to the reaction and the mixture is stirred 6 hours at room temperature. The reaction mixture is poured into 300 ml water and is extracted with 3×100 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 75 g silica gel (230-400 mesh), eluting with 40% acetone/hexane while collecting 9 ml fractions. Fractions 26-39 are combined and concentrated to afford 1.26 g (57%) of 4-Amino-6-chloro-2-(1-(3-isoquinolyl)ethyl)thio-pyrimidine as a white solid.

Workup

  1. stirringthe mixture is stirred 6 hours at room temperature
  2. extractionis extracted with 3×100 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 75 g silica gel (230-400 mesh)
  6. washeluting with 40% acetone/hexane
  7. customwhile collecting 9 ml fractions
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3ac6256bb5b24b3c83930ac3b8ec5af4
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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