Sodium Carbonate → (S)-4-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)-5-methoxy-N,N,N-trimethyl-5-oxopentan-1-aminium chloride

HRID 83837ノート

反応式

HRID 83837 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][C:28]([S:32]([OH:35])(=O)=[O:33])=[CH:27][C:26]=3[F:36])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:37][CH3:38].S(Cl)(Cl)=O.Cl.[Cl-].[NH2:45][C@H:46]([C:54]([O:56][CH3:57])=[O:55])[CH2:47][CH2:48][CH2:49][N+:50]([CH3:53])([CH3:52])[CH3:51].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CN(C=O)C>[Cl-:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][C:28]([S:32]([NH:45][C@H:46]([C:54]([O:56][CH3:57])=[O:55])[CH2:47][CH2:48][CH2:49][N+:50]([CH3:52])([CH3:51])[CH3:53])(=[O:33])=[O:35])=[CH:27][C:26]=3[F:36])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:37][CH3:38]

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 866622244-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzenesulfonic acidHCID 86702233(S)-4-amino-5-methoxy-N,N,N-trimethyl-5-oxopentan-1-aminium chloride hydrochloride

生成物 1

HCID 86702231(S)-4-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)-5-methoxy-N,N,N-trimethyl-5-oxopentan-1-aminium chloride収率 188.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

反応条件

温度
40 °C

実験手順

To 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzenesulfonic acid (1.2 g, 2.1 mmol, 1.1 eq) in DCM (6 mL) was added thionyl chloride (3 mL) followed by catalytic DMF (30 drops). After heating at 40° C. for 1 h, the reaction mixture was concentrated under reduced pressure and the resulting sulfonyl chloride was further dried on a high-vacuum pump for several hours. A solution of this sulfonyl chloride in MeCN (12 mL) was added to another flask containing (S)-4-amino-5-methoxy-N,N,N-trimethyl-5-oxopentan-1-aminium chloride hydrochloride (2.0 g, 7.5 mmol, 4.0 eq) and aq. Na2CO3 (2.0 g, 18.7 mmol, 10 eq, in 12 mL of water). The reaction mixture was stirred vigorously for 10 min. The organic layer was removed by pipette and concentrated to yield (S)-4-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)-5-methoxy-N,N,N-trimethyl-5-oxopentan-1-aminium chloride (1.56 g, over theoretical), which was used in the next step without purification. MS (EI) m/z 601 (M+).

後処理

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. dry with materialthe resulting sulfonyl chloride was further dried on a high-vacuum pump for several hours
  3. additionA solution of this sulfonyl chloride in MeCN (12 mL) was added to another flask
  4. customThe organic layer was removed by pipette
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-cf0f71e851044d34b042725c54ceb7fd
出典データセット
uspto-grants-2014_09
特許番号
US08846739B2

反応ノート

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