Cesium carbonate → HCID 178483017, compound

HRID 2173957Notes

Reaction equation

HRID 2173957 reaction equation
[C:1]([C:3]1[CH:37]=[CH:36][C:6]2[NH:7][C:8]([C:10]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][N:21]4C(OC(C)(C)C)=O)([NH:15][CH3:16])[C:11]([F:14])([F:13])[F:12])=[N:9][C:5]=2[CH:4]=1)#[N:2].C([O-])([O-])=O.[Cs+].[Cs+]>CO>[F:14][C:11]([F:12])([F:13])[C:10]([C:8]1[NH:7][C:6]2[CH:36]=[CH:37][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:9]=1)([C:17]1[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]2[C:18]=1[CH:19]=[CH:20][NH:21]2)[NH:15][CH3:16]

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 178483016HCID 178483016, compound

Product 1

HCID 178483017HCID 178483017, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (±)-tert-butyl 4-(1-(5-cyano-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-(methylamino)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (0.87 g, 1.69 mmol) in MeOH (16.94 mL) at room temperature, Cs2CO3 (2.76 g, 8.47 mmol) was added and the reaction was stirred at 60° C. After 2.5 hours the reaction was cooled to room temperature, quenched with aq. NH4Cl. The layers were separated and the aqueous layer was extracted with EtOAc. The organic layers were combined, dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-100% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6 with about 5 μL TFA) δ ppm 11.14 (br. s., 1H) 8.21 (br. s., 1H) 7.72 (d, J=8.46 Hz, 1H) 7.64 (dd, J=8.40, 1.45 Hz, 1H) 7.18 (t, J=2.84 Hz, 1H) 6.89 (s, 1H) 5.56 (br. s., 1H) 3.57 (br. s., 3H) 2.31 (s, 3H). HRMS calcd. for C21H18F3N5O (M+H)+ 414.1542. found 414.1542.

Workup

  1. temperatureAfter 2.5 hours the reaction was cooled to room temperature
  2. customquenched with aq. NH4Cl
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography (0-100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-e784b65fb1b54848ba49d7a8634653b4
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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