Hydrochloric Acid → n-[(1r)-1-[(4-Chlorophenyl)methyl]-2-(4-{2-[methyl-(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-(tert-butoxy)carboxamide

HRID 228096Notes

Reaction equation

HRID 228096 reaction equation
[CH3:1][N:2]([S:22]([CH3:25])(=[O:24])=[O:23])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]1.Cl.CCN(C(C)C)C(C)C.[NH:36]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C@@H:37]([C:46](O)=[O:47])[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=1.CCN=C=NCCCN(C)C.CI.C1C=NC2N(O)N=NC=2C=1>CCOC(C)=O.CN(C=O)C>[Cl:45][C:42]1[CH:43]=[CH:44][C:39]([CH2:38][C@@H:37]([NH:36][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C:46]([N:12]2[CH2:13][CH2:14][N:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[N:2]([CH3:1])[S:22]([CH3:25])(=[O:24])=[O:23])[CH2:10][CH2:11]2)=[O:47])=[CH:40][CH:41]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 10236463HCID 10236463, compoundHCID 21935145Tert-butyl 4-{2-[methyl(methylsulfonyl)amino]phenyl}piperazine-carboxylate

Product 1

HCID 21060076n-[(1r)-1-[(4-Chlorophenyl)methyl]-2-(4-{2-[methyl-(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-(tert-butoxy)carboxamideYield 31.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

tert-Butyl 4-{2-[methyl(methylsulfonyl)amino]phenyl}piperazinecarboxylate (Step 1) (700 mg, 1.9 mmol) was stirred with 25 mL of HCl satd EtOAc. The resulting crude material was diluted with EtOAc and washed with a satd NaHCO3 soln. The organic layer was separated, dried over Na2SO4, filtered and concentrated in vacuo. This material was treated with DIEA (400 μl, 2.295 mmol), Boc-p-Cl-D-Phe-OH (672 mg, 2.241 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (1.25 g, 4.206 mmol), HOAT (345 mg, 2.535 mmol), and DMF (15 mL) according to the procedure for preparation XIX. The crude material was purified by flash chromatography (SiO2, 1.5:1 hexane:EtOAc) to yield N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[methyl-(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-(tert-butoxy)carboxamide (327 mg). MS (ESI, pos. ion) m/z: 551 (M+H), (ESI, neg. ion) m/z: 549 (M−H). Calc'd for C26H35ClN4O5S: 551.10.

Workup

  1. washwashed with a satd NaHCO3 soln
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (SiO2, 1.5:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-2376d454dcd546e99561f27dded571fc
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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