1,2-Dichloroethane → HCID 86688736, compound

HRID 1752638Notes

Reaction equation

HRID 1752638 reaction equation
CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.C([O:28][C:29](=[O:34])[C@H:30]([CH2:32][OH:33])[NH2:31])C.C(CCC(N[C:44](=[O:68])[CH2:45][C:46]1[CH:50]=[C:49]([C:51]2[CH:56]=[CH:55][C:54]([S:57]([CH3:60])(=[O:59])=[O:58])=[CH:53][CH:52]=2)[N:48]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:47]=1[CH3:67])CO)(O)=O.[OH-].[Na+].Cl>C(Cl)Cl.CCO>[OH:33][CH2:32][C@H:30]([NH:31][C:44](=[O:68])[CH2:45][C:46]1[CH:50]=[C:49]([C:51]2[CH:52]=[CH:53][C:54]([S:57]([CH3:60])(=[O:59])=[O:58])=[CH:55][CH:56]=2)[N:48]([C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)[C:47]=1[CH3:67])[C:29]([OH:28])=[O:34]

Participants

10

Reactant 7

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 86688737HCID 86688737, compoundHCID 86688738HCID 86688738, compound

Product 1

HCID 86688736HCID 86688736, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

The following are added, at 0° C., to acid 6a (0.8 mmol) in DCM (10 ml): DIPEA (2.43 mmol), EDC (1.63 mmol), HOBt (0.27 mmol) and L-serine ethyl ester dihydrochloride (0.8 mmol). It is stirred at RT for 12 hours, then it is washed with H2O, the organic phase is separated, dried and concentrated. The residue is purified by chromatography (silica, EtOAc/MeOH (9:1)) obtaining: N-[1-(carboxyethyl)-2-hydroxyethyl]-2-[1-phenyl-2-methyl-5-(4-methanesulphonylphenyl)-1H-pyrrol-3-yl]-acetamide. Oil, yield 77%. 1H NMR (CDCl3) ppm: 1.25 (t, 3H); 2.05 (s, 3H); 2.70 (broad t, 1H); 2.97 (s, 3H); 3.51 (s, 2H); 3.93 (m, 2H); 4.20 (m, 2H); 4.63 (m, 1H), 6.48 (s, 1H); 6.74 (broad d, 1H), 7.11-7.16 (m, 4H); 7.37-7.40 (m, 3H); 7.60-7.64 (m, 3H). The carboxyethyl derivative (0.55 mmol) is treated with NaOH (0.55 mmol) in EtOH (5 ml), at 0° C., for 1 hour. It is acidified with 3N HCl to pH 6; the solvent is evaporated and the residue is taken up in EtOAc. The organic phase is washed until neutral with NaCl s.s., dried and concentrated. The residue is treated with EtOAc/n-hexane to give the product, m.p. 80-83° C., yield 50%. 1H NMR (DMSO-d6) ppm: 1.97 (s, 3H); 3.11 (s, 3H); 3.34 (s, 2H); 3.55-3.75 (m, 2H); 4.23-4.31 (m, 1H); 4.95-5.04 (s broad, 1H); 6.54 (s, 1H); 7.10-7.22 (m, 4H); 7.40-7.49 (m, 2H); 7.59-7.66 (m, 2H); 8.06-8.10 (broad d, 1H); 12.59 (broad s, 1H). MS ESI: m/z 455 (M−H+); m/z 495 (M+K+).

Workup

  1. washit is washed with H2O
  2. customthe organic phase is separated
  3. customdried
  4. concentrationconcentrated
  5. customThe residue is purified by chromatography (silica, EtOAc/MeOH (9:1))
  6. customobtaining
  7. customthe solvent is evaporated
  8. washThe organic phase is washed until neutral with NaCl s.s
  9. custom, dried
  10. concentrationconcentrated
  11. additionThe residue is treated with EtOAc/n-hexane
  12. customto give the product, m.p. 80-83° C., yield 50%

Sources & evidence

ORD record
ord-2d630b56f3934c1997b6813f9e2d2c2d
Source dataset
uspto-grants-2015_10
Patent number
US09162979B2

Reaction notes

Loading…