Hydrochloric Acid → HCID 178515380, compound

HRID 1096912Notes

Reaction equation

HRID 1096912 reaction equation
[CH:1]1([C:4]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:7]3[CH:15]=[CH:16][C:17]([C:19](OC)=[O:20])=[CH:18][C:6]=3[N:5]=2)[CH2:3][CH2:2]1.[OH-].[Na+].Cl.Cl.[NH:27]1[C:31]([C:32]2[CH:33]=[C:34]3[C:44](=[CH:45][CH:46]=2)[O:43][C:37]2([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:36][C:35]3=[O:47])=[N:30][N:29]=[N:28]1.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C1COCC1.CO.O.CN(C=O)C>[CH:1]1([C:4]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:7]3[CH:15]=[CH:16][C:17]([C:19]([N:40]4[CH2:41][CH2:42][C:37]5([CH2:36][C:35](=[O:47])[C:34]6[C:44](=[CH:45][CH:46]=[C:32]([C:31]7[NH:27][N:28]=[N:29][N:30]=7)[CH:33]=6)[O:43]5)[CH2:38][CH2:39]4)=[O:20])=[CH:18][C:6]=3[N:5]=2)[CH2:3][CH2:2]1

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66782575HCID 66782575, compoundHCID 178479612HCID 178479612, compound

Product 1

HCID 178515380HCID 178515380, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 2-cyclopropyl-1-phenyl-1H-benzimidazole-5-carboxylate (194 mg, 0.664 mmol) was dissolved in THF (6 mL) and MeOH (6 mL), and aqueous 5 N sodium hydroxide solution (0.66 mL, 3.30 mmol) was added to it and stirred at 60° C. for 2 hours. This was restored to room temperature, 5 N hydrochloric acid (0.66 mL, 3.30 mmol) was added thereto, the solvent was evaporated away under reduced pressure, and the residue was azeotroped with toluene. DMF (4 mL) and water (1 mL) were added to it, and 6-(tetrazol-5-yl)spiro[chroman-2,4′-piperidin]-4-one hydrochloride (256 mg, 0.797 mmol), triethylamine (0.14 mL, 0.996 mmol), HOBT (135 mg, 0.996 mmol) and WSC hydrochloride (191 mg, 0.996 mmol) were added thereto. The reaction liquid was stirred at 90° C. for 2 hours, restored to room temperature, and water was added thereto. The precipitated solid was taken out through filtration, and dried under reduced pressure to obtain the title compound as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ: 8.42 (1H, d, J=2.2 Hz), 8.23 (1H, dd, J=8.8, 2.2 Hz), 7.69-7.59 (6H, m), 7.34 (1H, d, J=8.8 Hz), 7.23 (1H, dd, J=8.4, 1.6 Hz), 7.14 (1H, d, J=8.4 Hz), 4.50-3.29 (5H, m), 2.98 (2H, s), 2.06-1.77 (4H, m), 1.15-1.11 (2H, m), 1.04-1.00 (2H, m). MS [M+H]+=546.

Workup

  1. customThis was restored to room temperature
  2. customthe solvent was evaporated away under reduced pressure
  3. customthe residue was azeotroped with toluene
  4. additionwere added
  5. customThe reaction liquid
  6. stirringwas stirred at 90° C. for 2 hours
  7. customrestored to room temperature
  8. filtrationThe precipitated solid was taken out through filtration
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-1fbf4ef97e74427981522cd036cbf70e
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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