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 83837Notes

Reaction equation

HRID 83837 reaction equation
[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]

Participants

7

Reactant 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

Product 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 chlorideYield 188.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-cf0f71e851044d34b042725c54ceb7fd
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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