Triethylamine → N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-propyl]-methanesulfonamide

HRID 1040794Notes

Reaction equation

HRID 1040794 reaction equation
[NH2:1][CH:2]([CH3:9])[CH2:3][NH:4][S:5]([CH3:8])(=[O:7])=[O:6].[Cl:10][C:11]1[N:16]=[C:15](Cl)[C:14]([Cl:18])=[CH:13][N:12]=1.CCN(CC)CC>C1COCC1>[Cl:10][C:11]1[N:16]=[C:15]([NH:1][CH:2]([CH3:9])[CH2:3][NH:4][S:5]([CH3:8])(=[O:7])=[O:6])[C:14]([Cl:18])=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2372592,4,5-TrichloropyrimidineHCID 63730869HCID 63730869, compound

Product 1

HCID 86633870N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-propyl]-methanesulfonamideYield 85.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-(2-Amino-propyl)-methanesulfonamide (325 mg, 2.14 mmol, 1.5 eq.) in THF (20 mL) was cooled to 0 C and 2,4,5-trichloropyrimidine (261 mg, 1.43 mmol, 162 μL, 1.0 eq.) was added. The reaction was stirred for 5 minutes and then NEt3 (711 mg, 7.04 mmol, 516 μL, 4.9 eq) was added. After 5 minutes, external cooling was removed and the reaction was stirred under a nitrogen atmosphere for 3 hours. The reaction was then partitioned between CH2Cl2 (30 mL) and sat. NaHCO3 (30 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (15 mL). The combined organic layers were dried (sodium sulfate), filtered, and concentrated under reduced pressure onto silica gel. Purification by silica gel chromatography (dry loaded) using a gradient of 0-10% MeOH/CH2Cl2 as the eluting solvent to obtain N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-propyl]-methanesulfonamide as a white solid (365 mg, 85%). m.p.=160° C.; LCMS (m/e) 299 (M+1); 1H-NMR (d6-DMSO, 400 MHz) δ 8.18 (s, 1H), 7.59-7.50 (m, 1H), 7.26-7.15 (m, 1H), 4.36-4.22 (m, 1H), 3.21-3.05 (m, 2H), 2.91 (s, 3H), 1.18 (d, 3H, J=6.6 Hz).

Workup

  1. additionwas added
  2. waitAfter 5 minutes
  3. temperatureexternal cooling
  4. customwas removed
  5. stirringthe reaction was stirred under a nitrogen atmosphere for 3 hours
  6. customThe reaction was then partitioned between CH2Cl2 (30 mL) and sat. NaHCO3 (30 mL)
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with CH2Cl2 (15 mL)
  9. dry with materialThe combined organic layers were dried (sodium sulfate)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure onto silica gel
  12. customPurification
  13. customby silica gel chromatography (dry loaded)

Sources & evidence

ORD record
ord-441e002751654668958b05269a7d8caa
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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