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

HRID 228096ノート

反応式

HRID 228096 の反応式
[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

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 10236463N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide methyliodideHCID 21935145Tert-butyl 4-{2-[methyl(methylsulfonyl)amino]phenyl}piperazine-carboxylate

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-2376d454dcd546e99561f27dded571fc
出典データセット
uspto-grants-2009_07
特許番号
US07560460B2

反応ノート

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