Hydrochloric Acid → HCID 178500186, compound

HRID 2174131Notes

Reaction equation

HRID 2174131 reaction equation
[C:1]([C:3]1[CH:47]=[CH:46][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:18]3[C:26]([O:27][CH3:28])=[CH:25][C:24]([CH3:29])=[C:23]4[C:19]=3[CH:20]=[CH:21][N:22]4COCC[Si](C)(C)C)([CH3:17])[CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[N:9][C:5]=2[CH:4]=1)#[N:2].C(C1C=CC2N=C(C(C3C(OC)=CC(C)=C4C=3C=CN4COCC[Si](C)(C)C)(C)CCC(OC)=O)N(COCC[Si](C)(C)C)C=2C=1)#N.Cl>CO>[C:1]([C:3]1[CH:47]=[CH:46][C:6]2[NH:7][C:8]([C:10]([C:18]3[C:26]([O:27][CH3:28])=[CH:25][C:24]([CH3:29])=[C:23]4[C:19]=3[CH:20]=[CH:21][NH:22]4)([CH3:17])[CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[N:9][C:5]=2[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid5×HCID 86701776HCID 86701776, compoundHCID 86701777HCID 86701777, compound

Product 1

HCID 178500186HCID 178500186, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent7×

Conditions

Temperature
65 °C

Procedure

(±)-Methyl 4-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-4-(5-methoxy-7-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-4-yl)pentanoate and (±)-methyl 4-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-4-(5-methoxy-7-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-4-yl)pentanoate (Example 155-K) (28 mg, 0.041 mmol) was dissolved in MeOH (700 μl) and then added 1.25 M HCl in MeOH (0.662 ml, 0.827 mmol) and heated at 65° C. After 30 minutes, an additional aliquot of 1.25 M HCl in MeOH (0.993 ml, 1.241 mmol) was added along with MeOH (700 uL) and the reaction left stirring for 17 hours. At this point an additional aliquot of 1.25 M HCl in MeOH (1.5 ml, 1.875 mmol) was added the reaction was heated at 75° C. for 3 hours and after additional 1.25 M HCl in MeOH (1.5 ml, 1.875 mmol) was added, the temperature was increased 85° C. and the reaction stirred for further 4 hours. At this point, an additional aliquot of 1.25 M HCl in MeOH (3 ml, 3.75 mmol) was added and the reaction was heated at 90° C. for 2 h. The reaction was then cooled to 0° C. and quenched with saturated sodium bicarbonate until pH=7 and then diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organics were dried over sodium sulfate and then concentrated. The resulting residue was absorbed onto silica to purify via FCC (0-60% EtOAc:heptanes) to obtain the title compound. MS (ESI+) m/z 417.18 (M+H).

Workup

  1. waitthe reaction left
  2. temperaturewas heated at 75° C. for 3 hours
  3. temperaturethe temperature was increased 85° C.
  4. stirringthe reaction stirred for further 4 hours
  5. temperaturethe reaction was heated at 90° C. for 2 h
  6. temperatureThe reaction was then cooled to 0° C.
  7. customquenched with saturated sodium bicarbonate until pH=7
  8. additiondiluted with EtOAc
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted with EtOAc
  11. dry with materialThe combined organics were dried over sodium sulfate
  12. concentrationconcentrated
  13. customThe resulting residue was absorbed onto silica
  14. customto purify via FCC (0-60% EtOAc:heptanes)

Sources & evidence

ORD record
ord-2307838b8f11450e91032c093422f935
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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