Phosphorus sulfide (P2S5) → 1-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbothioyl)-1h-benzimidazole

HRID 1796480Notes

Reaction equation

HRID 1796480 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)=O)=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH3:30])=[CH:24][CH:23]=2)[CH2:3][CH2:2]1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:32]>N1C=CC=CC=1>[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)=[S:32])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH3:30])=[CH:24][CH:23]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 14817Phosphorus sulfide (P2S5)HCID 221812751-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbonyl)-1H-benzimidazole

Product 1

HCID 221813481-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbothioyl)-1h-benzimidazole

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of free base 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbonyl)-1H-benzimidazole (Example 21, from 80 mg 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carboxylic acid) in pyridine (2 mL) was added P2S5 (507 mg, 1.14 mmol). The mixture was heated at 100° C. for 24 h and cooled to room temperature. After being decanted, the supernatant was concentrated and the residue was diluted with EtOAc (20 mL), washed with 1 N NaOH (2×10 mL) and then H2O (2×10 mL). The organic layer was dried over MgSO4 and was evaporated. The crude residue was purified by silica gel column chromatography to give an oil (59 mg, 62% for 2 steps). 1H NMR (400 MHz, CD3OD): δ 7.70 (s, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.12 (d, J=8.4 Hz, 2H), 6.81 (d, J=8.4 Hz, 2H), 4.27 (s, 2H), 4.08–3.95 (m, 4H), 3.89 (d, J=6.8 Hz, 2H), 3.57 (t, J=7.2 Hz, 2H), 2.14–2.03 (m, 2H), 2.00–1.92 (m, 2H), 1.38 (t, J=7.2 Hz, 3H), 1.06–0.98 (m, 1H), 0.54–0.48 (m, 2H), 0.28–0.22 (m, 2H). MS (ESI) (M+H)+=420.

Workup

  1. temperaturecooled to room temperature
  2. customAfter being decanted
  3. concentrationthe supernatant was concentrated
  4. additionthe residue was diluted with EtOAc (20 mL)
  5. washwashed with 1 N NaOH (2×10 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. customwas evaporated
  8. customThe crude residue was purified by silica gel column chromatography
  9. customto give an oil (59 mg, 62% for 2 steps)

Sources & evidence

ORD record
ord-8200743e42004e14a1d4b68ecd2e3aa5
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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