1-(4-Piperidinyl)-1H-benzimidazole → HCID 57253738, compound

HRID 1068155Notes

Reaction equation

HRID 1068155 reaction equation
[CH:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][N:5]([C@H:14]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[O:16])[CH2:4]1)=O.[NH:33]1[CH2:38][CH2:37][CH:36]([N:39]2[C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[N:41]=[CH:40]2)[CH2:35][CH2:34]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.CN(C=O)C>[N:39]1([CH:36]2[CH2:35][CH2:34][N:33]([CH2:1][C@@H:3]3[C@@H:7]([C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)[CH2:6][N:5]([C@H:14]([CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)[C:15]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)=[O:16])[CH2:4]3)[CH2:38][CH2:37]2)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[N:41]=[CH:40]1

Participants

6

Reactant 3

HCID 30192621-(4-Piperidinyl)-1H-benzimidazoleHCID 5049666Sodium triacetoxyborohydrideHCID 53654320HCID 53654320, compound

Product 1

HCID 57253738HCID 57253738, compoundYield 46.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 60 mg of α-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxy-benzyl ester (prepared above as Aldehyde 5) and 70 mg of 1-piperidin-4-yl-1-H-benzoimidazole (from Step C) in 4 mL THF and 1 mL of DMF was added 1 spatula tip of 4Å molecular sieves. After stirring at room temperature for 10 minutes, 80 mg sodium triacetoxyborohydride was added. Continued to stir at room temperature for another 10 hours. The reaction was concentrated and diluted with 20 ml of EtOAc and washed with 10 mL saturated NaHCO3 aqueous solution. After separating layers, the aqueous phas was extracted with 2×10 mL EtOAc. The combined organic phases were washed with 8 mL of brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with 100% EtOAc, then 90% EtOAc in CH3OH to give 40 mg of the title compound as an oil. 1H NMR (400 MHz, CDCl3): δ1.17-3.73 (m, 31H), 4.07 (m, 1H), 5.10(d, J=2.1 Hz, 2H), 6.86 (d, J=8.5, 2H), 7.16-7.36 (m, 10H), 7.78(m, 1H), 7.93(s. 1H). ESI-MS 621 (M+H); HPLC A: 2.96 min.

Workup

  1. stirringContinued to stir at room temperature for another 10 hours
  2. concentrationThe reaction was concentrated
  3. additiondiluted with 20 ml of EtOAc
  4. washwashed with 10 mL saturated NaHCO3 aqueous solution
  5. customAfter separating layers
  6. extractionthe aqueous phas was extracted with 2×10 mL EtOAc
  7. washThe combined organic phases were washed with 8 mL of brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography
  11. washeluting with 100% EtOAc

Sources & evidence

ORD record
ord-b9d27603b2ec48a4b37fb967754365f3
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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