Toluene → HCID 25235943, compound

HRID 1360746Notes

Reaction equation

HRID 1360746 reaction equation
[C:1](Cl)(Cl)=O.C1(C)C=CC=CC=1.[NH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.CCOP(O)N(C(C)C)C(C)C.[Cl:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[C:38]1[NH:39][C:40]2[CH:46]=[C:45]([C:47]([NH:49][NH2:50])=[O:48])[CH:44]=[CH:43][C:41]=2[N:42]=1>C(Cl)Cl.CCOC(C)=O.CN(C=O)C>[Cl:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[C:38]1[NH:39][C:40]2[CH:46]=[C:45]([C:47]3[O:48][C:1]([N:12]4[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]4)=[N:50][N:49]=3)[CH:44]=[CH:43][C:41]=2[N:42]=1

Participants

9

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 8082PiperidineHCID 1954513'-O-ethyl-N,N-diisopropylphosphoramiditeHCID 577865852-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 25235943HCID 25235943, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A 20% solution of phosgene in toluene (163 uL, 0.310 mmol) was added dropwise to a solution of piperidine (31 uL, 0.310 mmol) in DCM (2 mL) and EDIPA (108 uL, 0.620 mmol) at 0° C. under N2. The reaction was stirred for 40 min before the addition of 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (50 mg, 0.155 mmol) and DMF (1 mL). The ice in the ice bath was allowed to melt, slowly warming the reaction to room temp. The reaction was stirred for 4 days. The reaction was diluted with EtOAc (60 mL) and extracted with water (10 mL). The organic phase was concentrated to a yellow oil. The yellow oil was added to a microwave vial charged with THF (1.5 mL) and Burgess reagent. The mixture was heated by microwave irradiation to 150° C. for 15 min. The reaction was concentrated, and the concentrate diluted with water. The resulting precipitate was collected by filtration and purified by reverse-phase HPLC (25-60% ACN/H2O+5 mM NH4OH) to afford the title compound: 1H NMR (400 MHz, MeOD) δ ppm 1.74 (br. s., 6H) 3.57-3.64 (m, 4H) 7.55-7.63 (m, 3H) 7.78 (d, J=8.59 Hz, 1H) 7.94 (dd, J=8.53, 1.33 Hz, 1H) 8.20 (br. s., 1H); MS (m/z) 414.1 (M+1).

Workup

  1. temperatureslowly warming
  2. customthe reaction to room temp
  3. extractionextracted with water (10 mL)
  4. concentrationThe organic phase was concentrated to a yellow oil
  5. additionThe yellow oil was added to a microwave
  6. additionvial charged with THF (1.5 mL) and Burgess reagent
  7. concentrationThe reaction was concentrated
  8. additionthe concentrate diluted with water
  9. filtrationThe resulting precipitate was collected by filtration
  10. custompurified by reverse-phase HPLC (25-60% ACN/H2O+5 mM NH4OH)

Sources & evidence

ORD record
ord-71bb07a31af9444da6bbee3e483d36aa
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

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