1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (1RS,4aRS,7aRS)-6-{{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetyl}-4,4-diphenylperhydrothiopyrano[2,3-c]-pyrrole 1-oxide

HRID 375498Notes

Reaction equation

HRID 375498 reaction equation
O.OC1C2N=NNC=2C=CC=1.[C:12]1([C:18]2([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:26]3[CH:22]([CH2:23][NH:24][CH2:25]3)[S:21](=[O:27])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[N:34]1([CH2:39][CH:40]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[CH2:49][C:50](O)=[O:51])[CH3:41])[CH2:38][CH2:37][CH2:36][CH2:35]1.Cl.CN(C)CCCN=C=NCC>ClCCl>[N:34]1([CH2:39][CH:40]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[CH2:49][C:50]([N:24]2[CH2:25][CH:26]3[C:18]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:19][CH2:20][S:21](=[O:27])[CH:22]3[CH2:23]2)=[O:51])[CH3:41])[CH2:35][CH2:36][CH2:37][CH2:38]1

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18995289(-)-4,4-Diphenylperhydrothiopyrano[2,3-c]pyrrole 1-oxideHCID 54259613{[3-(1-Pyrrolidinyl)-2-propoxy]phenyl}acetic acidHCID 178526939HCID 178526939, compound

Product 1

HCID 67745327(1RS,4aRS,7aRS)-6-{{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetyl}-4,4-diphenylperhydrothiopyrano[2,3-c]-pyrrole 1-oxideYield 36.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

0.03 g of hydroxybenzotriazole hydrate is added to a solution, cooled to +5° C., of 0.69 g of (1RS,4aRS,7aRS)-4,4-diphenylperhydrothiopyrano[2,3-c]pyrrole 1-oxide and 0.68 g of {[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetic acid in 25 cm3 of dry dichloromethane, followed by a solution of 0.5 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 20 cm3 of dry dichloromethane. After stirring for 2 hours at +5° C. and 20 hours at 20° C., the reaction mixture is washed twice with 50 cm3 of distilled water and dried over magnesium sulphate and then concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 2.4 cm, height 32 cm), eluting under a nitrogen pressure of 0.8 bar with an ethyl acetate, acetic acid and water mixture (80/20/20 by volume) and collecting fractions of 25 cm3. Fractions 21 to 50 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from 8 cm3 of ethyl acetate, the crystals are washed with ethyl acetate and diisopropyl oxide and then dried. 0.45 g of (1RS,4aRS,7aRS)-6-{{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetyl}-4,4-diphenylperhydrothiopyrano[2,3-c]-pyrrole 1-oxide is obtained in the form of beige crystals; melting point 126° C.

Workup

  1. washthe reaction mixture is washed twice with 50 cm3 of distilled water
  2. dry with materialdried over magnesium sulphate
  3. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  4. customThe residue obtained
  5. customis chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 2.4 cm, height 32 cm)
  6. washeluting under a nitrogen pressure of 0.8 bar with an ethyl acetate, acetic acid and water mixture (80/20/20 by volume)
  7. customcollecting fractions of 25 cm3
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is crystallized from 8 cm3 of ethyl acetate
  10. washthe crystals are washed with ethyl acetate and diisopropyl oxide
  11. customdried

Sources & evidence

ORD record
ord-a7432ab92df845ac9c0112212f2bade7
Source dataset
uspto-grants-1996_01
Patent number
US05484942

Reaction notes

Loading…