Toluene → HCID 25235905, compound

HRID 1360745Notes

Reaction equation

HRID 1360745 reaction equation
[C:1](Cl)(Cl)=O.C1(C)C=CC=CC=1.[NH:12]1[CH2:17][CH2:16][O: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.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>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][O:15][CH2:14][CH2:13]4)=[N:50][N:49]=3)[CH:44]=[CH:43][C:41]=2[N:42]=1

Participants

10

Reactant 6

HCID 1140TolueneHCID 6371PhosgeneHCID 8083MorpholineHCID 1954513'-O-ethyl-N,N-diisopropylphosphoramiditeHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 577865852-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 25235905HCID 25235905, 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 morpholine (27 uL, 0.310 mmol) in DCM (3 mL) and EDIPA (108 uL, 0.620 mmol) at 0° C. The reaction was stirred for 25 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 transferred to a microwave vial charged with Burgess reagent (110 mg, 0.465 mmol) and the mixture heated by microwave irradiation to 150° C. for 15 min. The reaction was diluted with EtOAc (50 mL) and extracted with water (10 mL). The organic phase was concentrated to a yellow oil and purified by reverse-phase HPLC (20-45% ACN/H2O+5 mM NH4OH) to afford the title compound: 1H NMR (400 MHz, MeOD) δ ppm 3.66-3.72 (m, 4H) 3.90-3.96 (m, 4H) 7.63-7.72 (m, 3H) 7.87 (d, J=7.96 Hz, 1H) 8.03 (dd, J=8.59, 1.26 Hz, 1H) 8.30 (br. s., 1H); MS (m/z) 416.1 (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. custompurified by reverse-phase HPLC (20-45% ACN/H2O+5 mM NH4OH)

Sources & evidence

ORD record
ord-710ed188ce2a4db2931dd95595f918f1
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

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