3'-O-ethyl-N,N-diisopropylphosphoramidite → 2-(2,6-Dichloro-phenyl)-6-[5-(6-trifluoromethyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-yl]-1H-benzoimidazole

HRID 1360721Notes

Reaction equation

HRID 1360721 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][N:4]=1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=1[C:22]1[NH:23][C:24]2[CH:30]=[C:29]([C:31]([NH:33][NH2:34])=O)[CH:28]=[CH:27][C:25]=2[N:26]=1.CCOP(O)N(C(C)C)C(C)C.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1.CCOC(C)=O>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=1[C:22]1[NH:23][C:24]2[CH:30]=[C:29]([C:31]3[O:8][C:7]([C:6]4[CH:5]=[N:4][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:11][CH:10]=4)=[N:34][N:33]=3)[CH:28]=[CH:27][C:25]=2[N:26]=1

Participants

7

Reactant 4

HCID 1954513'-O-ethyl-N,N-diisopropylphosphoramiditeHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 27775576-(Trifluoromethyl)nicotinoyl chlorideHCID 577865852-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 252358162-(2,6-Dichloro-phenyl)-6-[5-(6-trifluoromethyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-yl]-1H-benzoimidazoleYield 57.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
150 °C

Procedure

6-Trifluoromethyl-nicotinoyl chloride (119 uL, 0.817 mmol) was added to a solution of 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (250 mg, 0.778 mmol) in THF (10 mL) and EDIPA (149 uL, 0.856 mmol). The reaction was stirred for 17 hr. The reaction was diluted with EtOAc (75 mL) and extracted with water (20 mL). The organic phase was dried over Na2SO4 and concentrated. The concentrate was taken up in DMF (3 mL) and transferred to a microwave vial charged with Burgess reagent (555 mg, 2.33 mmol). The reaction was heated to 150° C. for 15 min by microwave irradiation. The reaction was diluted with EtOAc (75 mL) and extracted with water (15 mL). The organic phase was dried over Na2SO4 and concentrated. The concentrate was purified by silica gel column chromatography (15-40% ACN/DCM) and the resulting colorless film triturated with MeOH/DCM to afford the title compound (214 mg): 1H NMR (400 MHz, DMSO-d6) δ ppm 7.64-7.68 (m, 1H) 7.71 (s, 1H) 7.73 (d, J=2.02 Hz, 1H) 7.83 (tautomer, d, J=8.46 Hz, 1H) 7.97 (tautomer, d, J=8.59 Hz, 1H) 8.12 (dd, J=14.15, 8.72 Hz, 1H) 8.21 (d, J=8.34 Hz, 1H) 8.41 (tautomer, s, 1H) 8.60 (tautomer, s, 1H) 8.85 (d, J=8.34 Hz, 1H) 9.54 (s, 1H) 13.41 (d, J=14.15 Hz, 1H); LCMS tR=1.53 min, MS (m/z) 476.7.

Workup

  1. extractionextracted with water (20 mL)
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated
  4. extractionextracted with water (15 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe concentrate was purified by silica gel column chromatography (15-40% ACN/DCM)
  8. customthe resulting colorless film triturated with MeOH/DCM

Sources & evidence

ORD record
ord-212f0f1c960f4591844a8374a2fd3625
Source dataset
uspto-grants-2011_02
Patent number
US07879850B2

Reaction notes

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