Acetic Acid → HCID 24829867, compound

HRID 1435131Notes

Reaction equation

HRID 1435131 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:39]=[CH:38][C:10]3[N:11]([C:14]4[S:18][C:17]([C:19]([NH2:21])=[O:20])=[C:16]([O:22][CH:23]([C:25]5[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH:32]6[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]6)[CH:26]=5)[CH3:24])[CH:15]=4)[CH:12]=[N:13][C:9]=3[CH:8]=2)[CH:4]=[N:3]1.[C:40](O)(=O)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(Cl)Cl.CO>[CH3:40][N:35]1[CH2:34][CH2:33][CH:32]([O:31][C:27]2[CH:26]=[C:25]([CH:23]([O:22][C:16]3[CH:15]=[C:14]([N:11]4[C:10]5[CH:38]=[CH:39][C:7]([C:5]6[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=6)=[CH:8][C:9]=5[N:13]=[CH:12]4)[S:18][C:17]=3[C:19]([NH2:21])=[O:20])[CH3:24])[CH:30]=[CH:29][CH:28]=2)[CH2:37][CH2:36]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 24829866HCID 24829866, compound

Product 1

HCID 24829867HCID 24829867, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(+/−)-5-[5-(1-Methyl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]-3-({1-[3-(4-piperidinyloxy)phenyl]ethyl}oxy)-2-thiophenecarboxamide (0.108 g, 0.199 mmol) was dissolved in 9 mL of DCM and 4.5 mL of MeOH with stirring. Acetic acid solution (0.24 mL, 1.0M in DCM, 0.24 mmol) and formaldehyde solution (0.030 mL, 37% in water, 0.40 mmol) were added. Sodium triacetoxyborohydride (0.0633 g, 0.299 mmol) was added in a single portion. The reaction was stirred for 1.5 h and poured into 1N aqueous NaOH solution. The mixture was extracted three times with 4:1 DCM/i-PrOH. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The solid was triturated with 1:1 ether/hexanes, filtered, and washed with hexanes. The solid was dried and collected to afford 0.099 g (90%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.51 (s, 1H), 8.17 (s, 1H), 7.93 (m, 1H), 7.90 (s, 1H), 7.75 (br s, 1H), 7.55 (dd, J=8.6, 1.5 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.42 (s, 1H), 7.26 (dd, J=7.9, 7.9 Hz, 1H), 7.12-7.07 (m, 2H), 7.05 (d, J=7.9 Hz, 1H), 6.85 (dd, J=7.9, 2.2 Hz, 1H), 5.69 (q, J=6.4 Hz, 1H), 4.30 (m, 1H), 3.84 (s, 3H), 2.57-2.43 (m, 2H), 2.09 (s, 3H), 2.10-2.00 (m, 2H), 1.88-1.78 (m, 2H), 1.67 (d, J=8.4 Hz, 3H), 1.60-1.47 (m, 2H). MS (ESI): 557 [M+H]+.

Workup

  1. extractionThe mixture was extracted three times with 4:1 DCM/i-PrOH
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe solid was triturated with 1:1 ether/hexanes
  6. filtrationfiltered
  7. washwashed with hexanes
  8. customThe solid was dried
  9. customcollected

Sources & evidence

ORD record
ord-bfb25bc2bd3d49949172a8267ec430e9
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

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