Hydrochloric Acid → HCID 178483019, compound

HRID 2173925Notes

Reaction equation

HRID 2173925 reaction equation
[F:1][C:2]([F:47])([F:46])[C:3]([C:27]1[N:31](COCC[Si](C)(C)C)[C:30]2[CH:40]=[CH:41][C:42]([C:44]#[N:45])=[CH:43][C:29]=2[N:28]=1)(O)[C:4]1[C:12]([S:13][CH3:14])=[CH:11][C:10]([CH3:15])=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17].FC(F)(F)C(C1N(COCC[Si](C)(C)C)C2C=C(C#N)C=CC=2N=1)(O)C1C(SC)=CC(C)=C2C=1C=[CH:54][N:55]2S(C1C=CC(C)=CC=1)(=O)=O.Cl.S(Cl)(Cl)=O.CN>CN(C=O)C>[F:47][C:2]([F:46])([F:1])[C:3]([C:27]1[NH:31][C:30]2[CH:40]=[CH:41][C:42]([C:44]#[N:45])=[CH:43][C:29]=2[N:28]=1)([C:4]1[C:12]([S:13][CH3:14])=[CH:11][C:10]([CH3:15])=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17])[NH:55][CH3:54]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 24386Thionyl ChlorideHCID 86701467HCID 86701467, compoundHCID 86701468HCID 86701468, compound

Product 1

HCID 178483019HCID 178483019, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Conditions

Temperature
60 °C

Procedure

To a mixture of (±)-2-(2,2,2-trifluoro-1-hydroxy-1-(7-methyl-5-(methylthio)-1-tosyl-1H-indol-4-yl)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-carbonitrile and (±)-2-(2,2,2-trifluoro-1-hydroxy-1-(7-methyl-5-(methylthio)-1-tosyl-1H-indol-4-yl)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-6-carbonitrile (Example 14-A) (0.37 g, 0.528 mmol) was added HCl (1.25M in MeOH, 4.22 mL, 5.28 mmol) and the mixture was stirred at 60° C. After 40 minutes the mixture was cooled to room temperature and concentrated. The residue was dissolved in CHCl3 (10.56 mL), and thionyl chloride (0.385 mL, 5.28 mmol) and a few drops of DMF were added and the mixture was heated at 70° C. After 2 hours the reaction was cooled to room temperature and concentrated. The residue was dissolved in methylamine (33% in EtOH, 6.57 mL, 52.8 mmol) and stirred at room temperature. After 5 minutes the reaction was concentrated and purified directly by flash chromatography (0-100% EtOAc in heptanes) to provide the title compound. MS (ESI+) m/z 584.2 (M+H).

Workup

  1. temperatureAfter 40 minutes the mixture was cooled to room temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in CHCl3 (10.56 mL)
  4. temperaturethe mixture was heated at 70° C
  5. temperatureAfter 2 hours the reaction was cooled to room temperature
  6. concentrationconcentrated
  7. stirringstirred at room temperature
  8. concentrationAfter 5 minutes the reaction was concentrated
  9. custompurified directly by flash chromatography (0-100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-75d8833c18694e8a90a013b08b4feb6f
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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