Acetic Anhydride → HCID 86633890, compound

HRID 1040903Notes

Reaction equation

HRID 1040903 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.[C:25](OC(=O)C)(=[O:27])[CH3:26]>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][C:25](=[O:27])[CH3:26])[C:13]([Cl:17])=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 438061,2-Diaminocyclohexane, trans-HCID 2372592,4,5-Trichloropyrimidine

Product 1

HCID 86633890HCID 86633890, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(1R,2R)-Cyclohexane-1,2-diamine (1.10 g, 9.68 mmol) was added into a Round bottom flask and was dissolved in Tetrahydrofuran (50 mL). The flask was cooled at 0° C., then 2,4,5-Trichloropyrimidine (1.60 g, 8.72 mmol) was added. A precipitate formed, and the reaction was stirred 10 min before Triethylamine (3.00 mL, 21.5 mmol) and Acetic anhydride (1.20 mL, 12.7 mmol) were added simultaneously via syringes. After 15 min, external cooling was removed, and the contents was stirred under an atmosphere of Nitrogen. After 45 min, the contents were partitioned between 100 mL DCM and 100 mL sat'd. sodium bicarbonate solution. The layers were separated, and the aqueous phase extracted once with 100 mL DCM. The organic fractions were washed once with 100 mL brine, dried (sodium sulfate) and then were concentrated onto 8 g Celite and chromatographed on an ISCO cartridge (120 g, 0-100% EA:Hex), with product beginning to elute at 75%. N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-acetamide was isolated as a white solid (1.08 g, 41%). m.p.=222-225° C.; LCMS (m/e) 303 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.99 (s, 1H), 6.30 (d, 1H, J=7 Hz), 5.69 (d, 1H, J=7.5 Hz), 3.83 (m, 2H), 2.25 (m, 1H), 2.04 (m, 1H), 1.90 (s, 3H), 1.80 (m, 2H), 1.33 (m, 4H).

Workup

  1. customA precipitate formed
  2. additionwere added simultaneously via syringes
  3. temperatureexternal cooling
  4. customwas removed
  5. waitAfter 45 min
  6. customthe contents were partitioned between 100 mL DCM and 100 mL
  7. customThe layers were separated
  8. extractionthe aqueous phase extracted once with 100 mL DCM
  9. washThe organic fractions were washed once with 100 mL brine
  10. dry with materialdried (sodium sulfate)
  11. concentrationwere concentrated onto 8 g Celite
  12. customchromatographed on an ISCO cartridge (120 g, 0-100% EA:Hex), with product
  13. washto elute at 75%

Sources & evidence

ORD record
ord-11a3028c8f5f4b0faca2da93df58fddf
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

Loading…