1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → tert-Butyl (2S)-2-{5-[1-(4-fluorophenyl)-2-(imidazol-1-yl)ethoxy]-2-(4-fluorophenethyl)benzoylamino}-4-methylsulfonylbutyrate

HRID 1251889ノート

反応式

HRID 1251889 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:25][CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[C:20]([CH:24]=2)[C:21](O)=[O:22])[CH2:9][N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)=[CH:4][CH:3]=1.[NH2:34][C@@H:35]([CH2:43][CH2:44][S:45]([CH3:48])(=[O:47])=[O:46])[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:25][CH2:26][C:27]3[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=3)=[C:20]([CH:24]=2)[C:21]([NH:34][C@@H:35]([CH2:43][CH2:44][S:45]([CH3:48])(=[O:47])=[O:46])[C:36]([O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:37])=[O:22])[CH2:9][N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 183244905-(1-(4-Fluorophenyl)-2-(imidazol-1-yl)ethoxy)-2-(4-fluorophenethyl)benzoic acidHCID 86585138Tert-butyl (2S)-2-amino-4-methanesulfonylbutanoate

生成物 1

HCID 57318515tert-Butyl (2S)-2-{5-[1-(4-fluorophenyl)-2-(imidazol-1-yl)ethoxy]-2-(4-fluorophenethyl)benzoylamino}-4-methylsulfonylbutyrate収率 74.4%

試薬・触媒・溶媒 1

HCID 142844-(Dimethylamino)pyridine触媒

実験手順

A mixture of 5-[(1-(4-fluorophenyl)-2-(imidazol-1-yl)ethoxy)]-2-(4-fluorophenethyl)benzoic acid (800 mg, 1.79 mmol), tert-butyl (2S)-2-amino-4-(methylsulfonyl)butanoate (L-methionine sulphone tert-butyl ester) (630 mg, 2.68 mmol), and DMAP (870 mg, 7.1 mmol), was treated with EDC.HCl (510 mg, 2.7 mmol) was stirred at ambient temperature for 16 hours. The reaction mixture was washed with aqueous citirc acid (1M, 2×), brine, dried (MgSO4) and evaporated to dryness. The residue was purified by chromatography on silica (40 gm Dynamax column, gradient elution 2-10% methanol/dichloromethane) to give a gum which, when triturated with diethyl ether/iso-hexane, gave the title compound as a cream solid (889 mg, 74%).

後処理

  1. washThe reaction mixture was washed with aqueous citirc acid (1M, 2×), brine
  2. dry with materialdried (MgSO4)
  3. customevaporated to dryness
  4. customThe residue was purified by chromatography on silica (40 gm Dynamax column, gradient elution 2-10% methanol/dichloromethane)
  5. customto give a gum which, when
  6. customtriturated with diethyl ether/iso-hexane

出典と根拠

ORDレコード
ord-6b6d27f5a05445b18b4205d9cfbcbc1a
出典データセット
uspto-grants-2002_01
特許番号
US06342765B1

反応ノート

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