Thiomorpholine → HCID 10231764, compound

HRID 25198Notes

Reaction equation

HRID 25198 reaction equation
CS([C:5]1(C)[C:8](=[C:9]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)[S:10]([CH3:13])(=[O:12])=[O:11])[CH2:7][N:6]1[C@H:22]([C:30]1[CH:35]=[CH:34][C:33]([CH2:36]Cl)=[CH:32][CH:31]=1)[C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)(=O)=O.[NH:39]1[CH2:44][CH2:43][S:42][CH2:41][CH2:40]1>ClCCl>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([C@@H:22]([C:30]2[CH:35]=[CH:34][C:33]([CH2:36][N:39]3[CH2:44][CH2:43][S:42][CH2:41][CH2:40]3)=[CH:32][CH:31]=2)[N:6]2[CH2:7][C:8](=[C:9]([C:14]3[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=3)[S:10]([CH3:13])(=[O:12])=[O:11])[CH2:5]2)=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 67164ThiomorpholineHCID 69799107HCID 69799107, compound

Product 1

HCID 10231764HCID 10231764, compoundYield 79.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The operation is carried out as described in Example 87, starting with 0.05 g of methylsulfonyl methyl 1-{(R*)-[4-(chloromethyl)phenyl](4-chlorophenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, 1.0 cm3 of dichloromethane and 0.025 g of thiomorpholine. The crude product is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 8 mm, height 8 cm), eluting with 80 cm3 of dichloromethane and then with a dichloromethane and methanol mixture (95/5 by volume), collecting 2.5 cm3 fractions immediately after using this eluent mixture. Fractions 3 to 8 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.038 g of 1-{(R*)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, form A isomer, is obtained in the form of a white foam [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): from 2.60 to 2.75 (mt, 8H), 2.80 (s, 3H), 3.44 (s, 2H), 3.84 (mt, 2H), 4.33 (mt, 2H), 4.50 (s, 1H), 6.83 (tt, J=8.5 and 2.5 Hz, 1H), 6.97 (mt, 2H), from 7.20 to 7.40 (mt, 8H)].

Workup

  1. customThe crude product is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 8 mm, height 8 cm)
  2. washeluting with 80 cm3 of dichloromethane
  3. customwith a dichloromethane and methanol mixture (95/5 by volume), collecting 2.5 cm3 fractions immediately
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-1795e1e4f6744f36a4fcc82d3b4acf51
Source dataset
uspto-grants-2005_02
Patent number
US06858603B2

Reaction notes

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