Ethylamine → (RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

HRID 25182Notes

Reaction equation

HRID 25182 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:11]2[CH2:14][C:13](=[C:15]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)[S:16]([CH3:19])(=[O:18])=[O:17])[CH2:12]2)=[CH:6][CH:5]=1)([OH:3])=O.Cl.C[NH:37][CH:38](N=C=NCC)[CH2:39]CNC.O.OC1C2N=NNC=2C=CC=1.C(N)C>C1COCC1.C(OCC)(=O)C.C1CCCCC1.ClCCl>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([CH:10]([C:7]2[CH:6]=[CH:5][C:4]([C:1](=[O:3])[NH:37][CH2:38][CH3:39])=[CH:9][CH:8]=2)[N:11]2[CH2:14][C:13](=[C:15]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)[S:16]([CH3:19])(=[O:17])=[O:18])[CH2:12]2)=[CH:33][CH:32]=1

Participants

9

Reactant 4

HCID 6341EthylamineHCID 22565413(RS)-1-{(4-carboxyphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidineHCID 230638721,3-Dimethylaminopropyl-3-ethylcarbodiimide hydrochlorideHCID 178526939HCID 178526939, compound

Product 1

HCID 10119284(RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidineYield 29.7%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The operation is carried out as in Example 52, starting with 1 g of (RS)-1-{(4-carboxyphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 0.38 g of 1,3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride, 22 mg of hydroxybenzotriazole hydrate, 30 cm3 of dichloromethane and 0.83 cm3 of a 2 M ethylamine solution in THF, chromatographing on a silica gel column (particle size 0.04-0.06 mm, diameter 4.1 cm, height 15 cm), at an argon pressure of 0.5 bar with a mixture of ethyl acetate and cyclohexane (45/55 by volume) as eluent and collecting 30 cm3 fractions. Fractions 22 to 32 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.29 g of (RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine is obtained in the form of a white solid [NMR spectrum in DMSO-d6, T=300K, δ in ppm (300 MHz): 1.07 (3H, t, J=6 Hz, CH3), 3.00 (3H, s, SCH3), 3.35 (2H, m, NCH2), 3.90 (2H, s, NCH2), 4.20 (2H, s, NCH2), 4.80 (1H, s, NCH), 7.15 (2H, d, J=8 Hz, 2CH arom.), 7.30 (1H, t, J=8 Hz, CH arom.), 7.35 (2H, d, J=7 Hz, 2CH arom.), 7.48 (4H, m, 4CH arom.), 7.74 (2H, d, J=7 Hz, 2CH arom.), 8.37 (1H, t, CONH)].

Workup

  1. customcollecting 30 cm3 fractions
  2. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-14838d78477e4cb19f07f59d37a716c9
Source dataset
uspto-grants-2005_02
Patent number
US06858603B2

Reaction notes

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