Methanol → HCID 178489074, compound

HRID 2173943Notes

Reaction equation

HRID 2173943 reaction equation
[C:1]([C:3]1[CH:44]=[CH:43][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:16]3[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]4[C:17]=3[CH:18]=[CH:19][N:20]4C(OC(C)(C)C)=O)([OH:15])[C:11]([F:14])([F:13])[F:12])=[N:9][C:5]=2[CH:4]=1)#[N:2].C(C1C=CC2N=C(C(C3C(OC)=CC(C)=C4C=3C=CN4C(OC(C)(C)C)=O)(O)C(F)(F)F)N(COCC[Si](C)(C)C)C=2C=1)#N.CO>Cl>[F:13][C:11]([F:12])([F:14])[C:10]([C:8]1[NH:7][C:6]2[CH:43]=[CH:44][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:9]=1)([OH:15])[C:16]1[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]2[C:17]=1[CH:18]=[CH:19][NH:20]2

Participants

5

Reactant 3

HCID 887MethanolHCID 86701501HCID 86701501, compoundHCID 86701502HCID 86701502, compound

Product 1

HCID 178489074HCID 178489074, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (2.2 g, 3.49 mmol) was dissolved in 1.25 M HCl in MeOH (55.8 mL, 69.8 mmol) and heated at 60° C. for 17 hours. The reaction was cooled to room temperature and the solvent was removed in vacuo. The resulting residue was diluted with MeOH and basified by adding NH4OH. The crude mixture was directly loaded onto a silica column and purified by flash chromatography (0-100% ethyl acetate in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6 with about 5 μL TFA) δ ppm 11.00 (br. s., 1H) 8.11 (s, 1H) 7.61-7.69 (m, 1H) 7.55-7.60 (m, 1H) 7.24 (t, J=2.84 Hz, 1H) 6.75 (s, 1H) 6.50 (br. s., 1H) 3.29 (s, 3H) 2.47 (d, J=0.51 Hz, 3H). HRMS calcd. for C20H16F3N4O2 (M+H)+ 401.122. found 401.1226.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customthe solvent was removed in vacuo
  3. additionThe resulting residue was diluted with MeOH
  4. additionby adding NH4OH
  5. custompurified by flash chromatography (0-100% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-1718002452cc4b91b9a35b8991908b7a
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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