Trifluoroacetic acid → HCID 178502061, compound

HRID 1875244Notes

Reaction equation

HRID 1875244 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[NH2:6][C:7]1[N:8](COCC[Si](C)(C)C)[C:9]([C:13]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([O:24][C:25]3[CH:30]=[C:29]([C:31]#[N:32])[CH:28]=[C:27]([Cl:33])[CH:26]=3)[C:18]=2[F:34])=[O:14])=[C:10]([Cl:12])[N:11]=1.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O.[BH4-].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:12][C:10]1[N:11]=[C:7]([NH:6][C:2](=[O:3])[O:4][CH3:5])[NH:8][C:9]=1[C:13]([NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([O:24][C:25]2[CH:30]=[C:29]([C:31]#[N:32])[CH:28]=[C:27]([Cl:33])[CH:26]=2)[C:18]=1[F:34])=[O:14]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 68724272HCID 68724272, compound

Product 1

HCID 178502061HCID 178502061, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Methyl chloroformate (0.020 mL, 0.26 mmol) was added to a solution of 2-amino-4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (0.050 g, 0.086 mmol) and DIEA (0.075 mL, 0.43 mmol) in CH2Cl2 (0.5 mL). The reaction mixture was stirred at RT overnight. TFA (0.5 mL) was added and the reaction mixture was stirred at RT for another 1 h. The reaction mixture was then evaporated and taken up in MeOH (1 mL). NaBH4 (0.030 g, 0.80 mmol) was added and the reaction mixture was stirred overnight. CH2Cl2 and sat'd NaHCO3 were added and the solution was extracted with CH2Cl2. The organic layer was dried (Na2SO4), filtered, concentrated and purified by Reverse-Phase HPLC (water:acetonitrile with 0.1% TFA) to afford the title compound (0.008 g, 19%) as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.56 (s, 1H) 7.34-7.44 (m, 2H) 7.25-7.29 (m, 1H) 7.24 (s, 1H) 4.57-4.70 (m, 2H) 3.81 (s, 3H). ES-LCMS: m/z 512.01, 513.97 (M+1).

Workup

  1. stirringthe reaction mixture was stirred at RT for another 1 h
  2. customThe reaction mixture was then evaporated
  3. stirringthe reaction mixture was stirred overnight
  4. additionwere added
  5. extractionthe solution was extracted with CH2Cl2
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by Reverse-Phase HPLC (water:acetonitrile with 0.1% TFA)

Sources & evidence

ORD record
ord-788325c0260840d3a6e9e1662b30a7e8
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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