Cesium carbonate → HCID 178489071, compound

HRID 2174100Notes

Reaction equation

HRID 2174100 reaction equation
[C:1]([C:3]1[CH:42]=[CH:41][C:6]2[NH:7][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][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([O-])([O-])=O.[Cs+].[Cs+]>CCO>[C:1]([C:3]1[CH:42]=[CH:41][C:6]2[NH:7][C:8]([C:10]([NH:15][CH2:16][C:17]([OH:19])=[O:18])([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][NH:26]4)[C:11]([F:12])([F:13])[F:14])=[N:9][C:5]=2[CH:4]=1)#[N:2]

Participants

4

Reactant 2

HCID 10796Cesium carbonate2×HCID 178472699HCID 178472699, compound

Product 1

HCID 178489071HCID 178489071, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (±)-tert-butyl 4-(1-(5-cyano-1H-benzo[d]imidazol-2-yl)-1-((2-ethoxy-2-oxoethyl)amino)-2,2,2-trifluoroethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (75 mg, 0.128 mmol) in EtOH (1.28 mL) at room temperature under nitrogen, Cs2CO3 (209 mg, 0.640 mmol) was added and the reaction was stirred at 60° C. After 95 minutes additional Cs2CO3 (209 mg, 0.640 mmol) was added. After 1 more hour the reaction was cooled, quenched with NH4Cl, extracted with EtOAc (×5), dried with MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-30% MeOH in DCM, MeOH contains 10% ammonium hydroxide) to provide the title compound as the ammonium salt. 1H NMR (ammonium salt, 400 MHz, DMSO-d6 with about 5 μL TFA) δ ppm 11.05 (br. s., 1H) 8.12 (br. s., 1H) 7.65 (d, J=8.08 Hz, 1H) 7.58 (dd, J=8.34, 1.52 Hz, 1H) 7.20 (br. s., 1H) 6.81 (s, 1H) 6.15 (br. s., 1H) 3.40 (br. s., 3H) 3.27 (d, J=17.43 Hz, 1H) 2.87 (d, J=17.31 Hz, 1H) 2.44-2.48 (m, 3H). HRMS calcd. for C22H18F3N5O3 (M+H)+ 458.1440. found 458.1418.

Workup

  1. temperatureAfter 1 more hour the reaction was cooled
  2. customquenched with NH4Cl
  3. extractionextracted with EtOAc (×5)
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash chromatography (0-30% MeOH in DCM, MeOH contains 10% ammonium hydroxide)

Sources & evidence

ORD record
ord-cc93e243fc964de3b125e279725a4640
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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