Hydrochloric Acid → HCID 178503113, compound

HRID 2173926Notes

Reaction equation

HRID 2173926 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=C[N:55]2S(C1C=CC(C)=CC=1)(=O)=O.Cl.S(Cl)(Cl)=O.C(O)C>CN(C=O)C.N>[NH2:55][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:20]=[CH:21][C:22]([CH3:23])=[CH:24][CH:25]=1)(=[O:17])=[O:18])[C:2]([F:47])([F:46])[F:1]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 24386Thionyl ChlorideHCID 86701467HCID 86701467, compoundHCID 86701468HCID 86701468, compound

Product 1

HCID 178503113HCID 178503113, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 222AmmoniaSolvent

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) (425 mg, 0.6 mmol) was added HCl (1.25M in MeOH, 4.85 mL, 6.06 mmol) and the mixture was stirred at 60° C. After 40 minutes the mixture was cooled to room temperature and concentrated. The mixture was dissolved in CHCl3 (12 mL), then was added thionyl chloride (0.44 mL, 6.06 mmol) and one drop of DMF and the mixture was heated at 70° C. After 4 hours the reaction was cooled to room temperature and stirred at room temperature overnight. The reaction was then concentrated, dissolved in ammonia in ethanol (2.0M, 30.3 mL, 60.6 mmol) and stirred at room temperature. After 15 minutes the reaction was concentrated and purified directly by flash chromatography (0-70% EtOAc in heptanes). MS (ESI+) m/z 570.3 (M+H).

Workup

  1. temperatureAfter 40 minutes the mixture was cooled to room temperature
  2. concentrationconcentrated
  3. dissolutionThe mixture was dissolved in CHCl3 (12 mL)
  4. temperaturethe mixture was heated at 70° C
  5. temperatureAfter 4 hours the reaction was cooled to room temperature
  6. stirringstirred at room temperature overnight
  7. concentrationThe reaction was then concentrated
  8. stirringstirred at room temperature
  9. concentrationAfter 15 minutes the reaction was concentrated
  10. custompurified directly by flash chromatography (0-70% EtOAc in heptanes)

Sources & evidence

ORD record
ord-b17aab849f934ee8aa7186022bb9b605
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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