Methanol → HCID 178489069, compound

HRID 2173955Notes

Reaction equation

HRID 2173955 reaction equation
[C:1]([C:3]1[CH:50]=[CH:49][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:22]3[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4C(OC(C)(C)C)=O)([NH:15]S(C(C)(C)C)=O)[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)(NS(C(C)(C)C)=O)C(F)(F)F)N(COCC[Si](C)(C)C)C=2C=1)#N.CO.C([O-])([O-])=O.[Cs+].[Cs+]>Cl.[NH4+].[Cl-]>[NH2:15][C:10]([C:8]1[NH:7][C:6]2[CH:49]=[CH:50][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:9]=1)([C:22]1[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]2[C:23]=1[CH:24]=[CH:25][NH:26]2)[C:11]([F:14])([F:13])[F:12]

Participants

7

Reactant 4

HCID 887MethanolHCID 10796Cesium carbonate2×HCID 86701518HCID 86701518, compoundHCID 86701519HCID 86701519, compound

Product 1

HCID 178489069HCID 178489069, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 25517Ammonium ChlorideSolvent

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)-1-(1,1-dimethylethylsulfinamido)-2,2,2-trifluoroethyl)-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)-1-(1,1-dimethylethylsulfinamido)-2,2,2-trifluoroethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (0.50 g, 0.68 mmol) was dissolved in 1.25M HCl in MeOH (10.9 mL, 13.63 mmol) and the mixture was heated at 60° C. After 4 hours the reaction was cooled to room temperature and concentrated. The residue was dissolved in MeOH (6.81 mL) and Cs2CO3 (2.22 g, 6.81 mmol) was added, and the mixture was stirred at 60° C. After 30 minutes additional Cs2CO3 (1.11 g, 3.4 mmol) was added. After 10 minutes the reaction was diluted with sat. aq. NH4Cl and the layers separated. The aqueous layer was extracted with EtOAc, dried over MgSO4, filtered and concentrated. The resulting residues was purified by flash column chromatography (0-100% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6 with about 5 μL TFA) δ ppm 11.19 (br. s., 1H) 8.27 (br. s., 1H) 7.78 (d, J=7.96 Hz, 1H) 7.69 (dd, J=8.46, 1.52 Hz, 1H) 7.13 (t, J=2.91 Hz, 1H) 6.94 (s, 1H) 5.09 (br. s., 1H) 3.77 (s, 3H). HRMS calcd. for C20H16F3N6O (M+H)+ 400.138. found 400.1385.

Workup

  1. temperatureAfter 4 hours the reaction was cooled to room temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in MeOH (6.81 mL)
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residues was purified by flash column chromatography (0-100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-c3580ae03fe744b2ae6ff28418572c0a
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

Loading…