Acetic Acid → HCID 57937496, compound

HRID 1435120Notes

Reaction equation

HRID 1435120 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:15]([O:17][C:18]1[CH:22]=[C:21]([N:23]2[C:27]3[CH:28]=[CH:29][C:30]([C:32]4[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=4)=[CH:31][C:26]=3[N:25]=[CH:24]2)[S:20][C:19]=1[C:38]([NH2:40])=[O:39])[CH3:16].C=O.[C:43](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[Cl:1][C:2]1[C:7]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH3:43])[CH2:11][CH2:10]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:15]([O:17][C:18]1[CH:22]=[C:21]([N:23]2[C:27]3[CH:28]=[CH:29][C:30]([C:32]4[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=4)=[CH:31][C:26]=3[N:25]=[CH:24]2)[S:20][C:19]=1[C:38]([NH2:40])=[O:39])[CH3:16]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 24831630HCID 24831630, compound

Product 1

HCID 57937496HCID 57937496, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-({(1R)-1-[2-chloro-3-(4-piperidinyloxy)phenyl]ethyl}oxy)-5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]-2-thiophenecarboxamide (Example 47, 230 mg, 0.40 mmol) in DCM (4 mL) and MeOH (2 mL) was added formaldehyde (0.033 mL, 1.2 mmol) and acetic acid (0.046 mL, 0.80 mmol) followed by sodium triacetoxy borohydride (0.17 g, 0.80 mmol). The solution was stirred for 1 h. The solution was diluted with DCM (20 mL) and washed with sat'd NaHCO3 solution (10 mL). The organic layers were dried (MgSO4), filtered and the solvent removed on a rotovap. The residue was dissolved in DCM and loaded onto a 4 g ISCO chromatography column and eluted with a gradient of 100:0 to 30:70 DCM : (80:20:2 DCM:MeOH:ammonium hydroxide) over 20 min. The appropriate fractions were combined and the solvent removed to provide 0.20 g of the title compound as a white solid (85 %). 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.88 (s, 1H), 7.79 (s, 1H), 7.65 (s, 1H), 7.45 (d, J=1.1 Hz, 2H), 7.30-7.22 (m, 2H), 7.06 (d, J=7.9 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H), 6.74 (bs, 1H), 6.64 (s, 1H), 5.91 (q, J=6.4 Hz, 1H), 4.45-4.38 (m, 1H), 3.97 (s, 3H), 2.71-2.61 (m, 2H), 2.47-2.27 (m, 2H), 2.29 (s, 3H), 2.05-1.87 (m, 4H), 1.77 (d, J=6.4 Hz, 3H). MS (ESI): 591 [M+H]+.

Workup

  1. washwashed with sat'd NaHCO3 solution (10 mL)
  2. dry with materialThe organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent removed on a rotovap
  5. dissolutionThe residue was dissolved in DCM
  6. washeluted with a gradient of 100:0 to 30:70 DCM
  7. wait(80:20:2 DCM:MeOH:ammonium hydroxide) over 20 min
  8. customthe solvent removed

Sources & evidence

ORD record
ord-686d838ae2fd4f778e3d25295f7ffea0
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

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