Hydrochloric Acid → HCID 178435869, compound

HRID 2174040Notes

Reaction equation

HRID 2174040 reaction equation
[C:1]([C:3]1[CH:53]=[CH:52][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:22]3[C:30]([CH2:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4S(C3C=CC(C)=CC=3)(=O)=O)([O:15][CH2:16][C:17]([O:19]CC)=[O:18])[C:11]([F:14])([F:13])[F:12])=[N:9][C:5]=2[CH:4]=1)#[N:2].C(C1C=CC2N=C(C(C3C(CC)=CC(C)=C4C=3C=CN4S(C3C=CC(C)=CC=3)(=O)=O)(OCC(OCC)=O)C(F)(F)F)N(COCC[Si](C)(C)C)C=2C=1)#N.Cl.[OH-].[K+]>CCO>[C:1]([C:3]1[CH:53]=[CH:52][C:6]2[NH:7][C:8]([C:10]([C:22]3[C:30]([CH2:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]4[C:23]=3[CH:24]=[CH:25][NH:26]4)([O:15][CH2:16][C:17]([OH:19])=[O:18])[C:11]([F:12])([F:13])[F:14])=[N:9][C:5]=2[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 86701663HCID 86701663, compoundHCID 86701664HCID 86701664, compound

Product 1

HCID 178435869HCID 178435869, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of a mixture of (±)-ethyl 2-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-1-(5-ethyl-7-methyl-1-tosyl-1H-indol-4-yl)-2,2,2-trifluoroethoxy)acetate and (±)-ethyl 2-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-1-(5-ethyl-7-methyl-1-tosyl-1H-indol-4-yl)-2,2,2-trifluoroethoxy)acetate (153 mg, 0.199 mmol) and HCl (1.25 M in MeOH) (1592 μL, 1.990 mmol) was allowed to stir at 60° C. for 0.5 h. The reaction was cooled to rt and concentrated. A suspension of the residue and KOH (112 mg, 1.99 mmol) in EtOH (2 mL) was allowed to stir at 100° C. for 1 h under microwave irradiation. The reaction mixture was concentrated. The crude was purified by HPLC (HC-A) to give the title compound. 1H NMR (TFA salt, 400 MHz, CD3OD) δ 8.05 (s, 1H), 7.71 (br. d, J=8.34 Hz, 1H), 7.61 (dd, J=1.51, 8.59 Hz, 1H), 7.06 (br. s, 1H), 6.92 (s, 1H), 6.11 (br. s, 1H), 4.17 (d, J=16.17 Hz, 1H), 3.95 (d, J=16.17 Hz, 1H), 2.70-2.85 (br. m, 1H), 2.49 (s, 3H), 2.33-2.44 (br. m, 1H) 1.06 (br. t, 3H). HRMS calcd. for C23H19F3N4O3 (M+H)+ 457.1488. found 457.1474.

Workup

  1. temperatureThe reaction was cooled to rt
  2. concentrationconcentrated
  3. stirringto stir at 100° C. for 1 h under microwave irradiation
  4. concentrationThe reaction mixture was concentrated
  5. customThe crude was purified by HPLC (HC-A)

Sources & evidence

ORD record
ord-7cc94842dd9b46d89b9e1b45fb175e3c
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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