Toluene → HCID 25235944, compound

HRID 1360747Notes

Reaction equation

HRID 1360747 reaction equation
C(Cl)(Cl)=O.C1(C)C=CC=CC=1.N1CCCC1.CCOP(O)N(C(C)C)C(C)C.[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=1[C:37]1[NH:38][C:39]2[CH:45]=[C:44]([C:46]([NH:48][NH2:49])=[O:47])[CH:43]=[CH:42][C:40]=2[N:41]=1.[CH3:50][CH2:51][N+:52](S(N=C(OC)[O-])(=O)=O)([CH2:55][CH3:56])[CH2:53]C>C1COCC1.CN1C(=O)CCC1>[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=1[C:37]1[NH:38][C:39]2[CH:45]=[C:44]([C:46]3[O:47][C:53]([N:52]4[CH2:55][CH2:56][CH2:50][CH2:51]4)=[N:49][N:48]=3)[CH:43]=[CH:42][C:40]=2[N:41]=1

Participants

9

Reactant 6

HCID 1140TolueneHCID 6371PhosgeneHCID 31268PyrrolidineHCID 1954513'-O-ethyl-N,N-diisopropylphosphoramiditeHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 577865852-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 25235944HCID 25235944, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

A 20% solution of phosgene in toluene (163 uL, 0.310 mmol) was added dropwise to a solution of pyrrolidine (51 uL, 0.620 mmol) in THF (2 mL) and EDIPA (216 uL, 1.24 mmol) at 0° C. under N2. The reaction was stirred for 20 min before the addition of 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (100 mg, 0.310 mmol) and NMP (1 mL). The ice bath was removed after 2 hr and the reaction allowed to stir overnight. The reaction was heated to 60° C. for 1.5 hr before being concentrated. The concentrate was added to a microwave vial charged with Burgess reagent (220 mg, 0.930 mmol) and the mixture heated to 150° C. for 15 min by microwave irradiation. The reaction was partitioned between EtOAc and H2O. The organic phase was concentrated and purified by reverse phase HPLC (25-50% ACN/H2O+5 mM NH4OH) to afford the title compound: 1H NMR (400 MHz, MeOD) δ ppm 2.05-2.14 (m, 4H) 3.58-3.67 (m, 4H) 7.55-7.64 (m, 3H) 7.79 (br. s., 1H) 7.94 (d, J=8.34 Hz, 1H) 8.19 (br. s., 1H); MS m/z=400.1 (M+1).

Workup

  1. customThe ice bath was removed after 2 hr
  2. concentrationbefore being concentrated
  3. additionThe concentrate was added to a microwave
  4. temperaturethe mixture heated to 150° C. for 15 min by microwave irradiation
  5. customThe reaction was partitioned between EtOAc and H2O
  6. concentrationThe organic phase was concentrated
  7. custompurified by reverse phase HPLC (25-50% ACN/H2O+5 mM NH4OH)

Sources & evidence

ORD record
ord-739dc3684b6744cbac13f03925aa0612
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

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