Methanesulfonamide → HCID 56591193, compound

HRID 1048247Notes

Reaction equation

HRID 1048247 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[C@H:10]([CH2:26][C:27](O)=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:30][S:31]([NH2:34])(=[O:33])=[O:32].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:23][CH2:24]3)[C:11](=[O:25])[C@H:10]([CH2:26][C:27]([NH:34][S:31]([CH3:30])(=[O:33])=[O:32])=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 56591348HCID 56591348, compound

Product 1

HCID 56591193HCID 56591193, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetic acid (Example 41) (83 mg, 0.192 mmol), methanesulfonamide (22.59 mg, 0.230 mmol) and 4-dimethylaminopyridine (1.057 mg, 0.00865 mmol) in DCM (2 mL) was added diisopropylethylamine (80 μL, 0.461 mmol). The reaction mixture was stirred at room temperature for one minute before adding bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (125 mg, 0.269 mmol). The reaction mixture was stirred at room temperature for 3 hours. The reaction was quenched with 1N HCl and the aqueuos layer was extracted with DCM (10 mL). The combined organic layers were washed with 1N HCl, 1N NaOH, sat. aq. NaCl solution and concentrated under reduced pressure. The residue was purified by reversed phase preparatory HPLC (column: Gemini-NX C18 5 μm column; Phenomonex, Torrance, Calif.; eluent: 0 to 100% MeCN+0.1% TFA in water+0.1% TFA, over 20 minutes) to afford the title compound.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 hours
  2. customThe reaction was quenched with 1N HCl
  3. extractionthe aqueuos layer was extracted with DCM (10 mL)
  4. washThe combined organic layers were washed with 1N HCl, 1N NaOH, sat. aq. NaCl solution
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by reversed phase preparatory HPLC (column: Gemini-NX C18 5 μm column; Phenomonex, Torrance, Calif.; eluent: 0 to 100% MeCN+0.1% TFA in water+0.1% TFA, over 20 minutes)

Sources & evidence

ORD record
ord-6dc02977c63c4b689ff13ae49833cf3b
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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