Pyridine → HCID 86762244, compound

HRID 338154Notes

Reaction equation

HRID 338154 reaction equation
[C:1]([C:3]1[S:7][C:6]([C@:8]23[CH2:16][N:15]([C:17]4[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=4)[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:24]C(=O)C2C=CC=CC=2)=[N:9]3)=[CH:5][CH:4]=1)#[N:2].N1C=CC=CC=1.Cl.CON>C(O)C>[NH2:24][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:14][N:15]([C:17]3[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=3)[CH2:16][C@:8]2([C:6]2[S:7][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[N:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 86762245HCID 86762245, compound

Product 1

HCID 86762244HCID 86762244, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
55 °C

Procedure

To N-[(4aR,7aR)-7a-(5-cyanothiophen-2-yl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (442 mg, 0.951 mmol) in ethanol (19 mL) is added pyridine (752.6 mg, 9.5 mmol) and O-methylhydroxylamine HCl (794.6 mg, 9.5 mmol). The mixture is heated to 55° C. under an atmosphere of nitrogen for 12 hours. The mixture is concentrated, dissolved in dichloromethane and concentrated again. The residue is dissolved in ethyl acetate and water and washed with saturated aqueous NaHCO3. The phases are separated and the aqueous phase extracted with ethyl acetate (30 mL). The organic phases are combined, dried over Na2SO4, filtered, and concentrated. The residue is purified with silica gel chromatography eluting with a 70:30 to 0:100 hexane/ethyl acetate gradient. The isolated product is repurified with silica gel chromatography eluting with 70:30 dichloromethane/ethyl acetate for 20 minutes and then a gradient to 0:100 to give the title product (294 mg, 86%). ES/MS (m/e): 361 (M+H).

Workup

  1. concentrationThe mixture is concentrated
  2. dissolutiondissolved in dichloromethane
  3. concentrationconcentrated again
  4. dissolutionThe residue is dissolved in ethyl acetate
  5. washwater and washed with saturated aqueous NaHCO3
  6. customThe phases are separated
  7. extractionthe aqueous phase extracted with ethyl acetate (30 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue is purified with silica gel chromatography
  12. washeluting with a 70:30 to 0:100 hexane/ethyl acetate gradient
  13. customThe isolated product is repurified with silica gel chromatography
  14. washeluting with 70:30 dichloromethane/ethyl acetate for 20 minutes

Sources & evidence

ORD record
ord-f22ef2902efc48b88bff834d91546a6c
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

Loading…