Triethylamine → N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

HRID 1040895Notes

Reaction equation

HRID 1040895 reaction equation
[C@@H:1]1([NH2:8])[CH2:6][CH2:5][CH2:4][CH2:3][C@H:2]1[NH2:7].[Cl:9][C:10]1[N:15]=[C:14](Cl)[C:13]([Cl:17])=[CH:12][N:11]=1.C(N(CC)CC)C.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>O1CCCC1>[Cl:9][C:10]1[N:15]=[C:14]([NH:7][C@@H:2]2[CH2:3][CH2:4][CH2:5][CH2:6][C@H:1]2[NH:8][S:26]([CH3:25])(=[O:28])=[O:27])[C:13]([Cl:17])=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 438061,2-Diaminocyclohexane, trans-HCID 2372592,4,5-Trichloropyrimidine

Product 1

HCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(1R,2R)-Cyclohexane-1,2-diamine (4.17 g, 36.5 mmol) was added into a round bottom flask and was dissolved in tetrahydrofuran (200 mL). The flask was cooled at 0° C., then 2,4,5-trichloropyrimidine (6.08 g, 33.1 mmol) was added. A precipitate formed, and the reaction was stirred 5 min before triethylamine (12 mL, 83 mmol) and methanesulfonyl chloride (4.00 mL, 51.7 mmol) were added simultaneously via two syringes. After 5 min, external cooling was removed, and the contents were stirred under an atmosphere of nitrogen. After 45 min, the contents were partitioned between dichloromethane (150 mL) and saturated sodium bicarbonate solution (150 mL). The layers were separated, and the aqueous phase extracted with dichloromethane (100 mL). The organic fractions were washed with brine (100 mL), dried (sodium sulfate) and were concentrated onto 37 g silica gel, and chromatographed on an ISCO cartridge (120 g SiO2, 0-50% EA:Hex). N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide was isolated as a white solid (4.8 g, 43%). m.p. 163-166° C.; LCMS (m/e) 339 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 5.91 (d, 1H, J=7.6 Hz), 5.91 (d, 1H, J=7.6 Hz), 5.91 (d, 1H, J=7.6 Hz), 3.32 (m, 1H), 3.91 (m, 1H), 2.92 (s, 3H), 2.25 (d, 1H, J=12 Hz), 2.13 (d, 1H, J=12 Hz), 1.83 (m, 2H), 1.25-1.48 (m, 4H).

Workup

  1. customA precipitate formed
  2. additionwere added simultaneously via two syringes
  3. temperatureexternal cooling
  4. customwas removed
  5. waitAfter 45 min
  6. customthe contents were partitioned between dichloromethane (150 mL) and saturated sodium bicarbonate solution (150 mL)
  7. customThe layers were separated
  8. extractionthe aqueous phase extracted with dichloromethane (100 mL)
  9. washThe organic fractions were washed with brine (100 mL)
  10. dry with materialdried (sodium sulfate)
  11. concentrationwere concentrated onto 37 g silica gel
  12. customchromatographed on an ISCO cartridge (120 g SiO2, 0-50% EA:Hex)

Sources & evidence

ORD record
ord-b65167b0ada3464bbe5950c32045aab1
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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