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

HRID 1687109Notes

Reaction equation

HRID 1687109 reaction equation
[NH2:1][C:2]([CH3:10])([CH3:9])[CH2:3][NH:4][S:5]([CH3:8])(=[O:7])=[O:6].[Cl:11][C:12]1[N:17]=[C:16](Cl)[C:15]([Cl:19])=[CH:14][N:13]=1.CCN(CC)CC>C1COCC1>[Cl:11][C:12]1[N:17]=[C:16]([NH:1][C:2]([CH3:10])([CH3:9])[CH2:3][NH:4][S:5]([CH3:8])(=[O:7])=[O:6])[C:15]([Cl:19])=[CH:14][N:13]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2372592,4,5-TrichloropyrimidineHCID 54269131HCID 54269131, compound

Product 1

HCID 86633871N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-2-methyl-propyl]-methanesulfonamideYield 48.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

N-(2-Amino-2-methyl-propyl)-methanesulfonamide (1.15 g, 6.90 mmol, 1.2 eq.) in THF (20 mL) was cooled to 0° C. and 2,4,5-trichloropyrimidine (1.05 g, 5.75 mmol, 656 μL, 1.0 eq.) was added. The reaction was stirred for 5 minutes and then NEt3 (2.07 mL) was added. After 5 minutes, external cooling was removed and the reaction was heated at 60° C. overnight under a nitrogen atmosphere. The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (75 mL). The combined organic layers were dried (sodium sulfate), filtered, and concentrated under reduced pressure onto basic alumina. Purification by basic alumina chromatography (dry loaded) using a gradient of 0-60% EtOAc/hex as the eluting solvent to obtain N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-2-methyl-propyl]-methanesulfonamide as a white solid (868 mg, 48%). m.p.=156-158° C.; LCMS (m/e) 313 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 5.57 (bs, 1H), 5.25-5.16 (m, 1H), 3.54 (d, 2H, J=6.8 Hz), 3.00 (s, 3H), 1.53 (s, 6H).

Workup

  1. waitAfter 5 minutes
  2. temperatureexternal cooling
  3. customwas removed
  4. customThe reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with CH2Cl2 (75 mL)
  7. dry with materialThe combined organic layers were dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure onto basic alumina
  10. customPurification
  11. customby basic alumina chromatography (dry loaded)

Sources & evidence

ORD record
ord-86694a75e6324bea8cf9cf34b98ea4f0
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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