1-Methylpiperazine → HCID 86691664, compound

HRID 85085Notes

Reaction equation

HRID 85085 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:18]4[C:13](=[N:14][CH:15]=[C:16]([C:19]5[CH:26]=[CH:25][C:22]([CH:23]=O)=[C:21]([C:27]([F:30])([F:29])[F:28])[CH:20]=5)[CH:17]=4)[N:12](S(C4C=CC(C)=CC=4)(=O)=O)[CH:11]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH3:41][N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:18]4[C:13](=[N:14][CH:15]=[C:16]([C:19]5[CH:26]=[CH:25][C:22]([CH2:23][N:45]6[CH2:46][CH2:47][N:42]([CH3:41])[CH2:43][CH2:44]6)=[C:21]([C:27]([F:29])([F:30])[F:28])[CH:20]=5)[CH:17]=4)[NH:12][CH:11]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 86691665HCID 86691665, compound

Product 1

HCID 86691664HCID 86691664, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[3-(1H-indol-5-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-trifluoromethyl-benzaldehyde (0.12 g, 0.214 mmol) in CH2Cl2 (3 mL) was added 1-methylpiperazine (32 mL, 0.32 mmol) and sodium triacetoxyborohydride (136 mg, 0.64 mmol). The reaction mixture was stirred for 1 hr at room temperature, after which it was partitioned between CH2Cl2 and 1 M NaOH. The organic layer was separated, dried over MgSO4, and concentrated in vacuo. The residue was dissolved in 3:2 MeOH:acetone (5 mL), and 2 M NaOH (1.5 mL) was added. The resulting mixture was stirred at 65° C. for 30 min, after which it was partitioned between EtOAc and 1 M NaOH. The organic layer was separated, dried over MgSO4, filtered, and stripped to provide a residue that was subjected to silica gel column to yield 3-(1H-indol-5-yl)-5-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-1H-pyrrolo[2,3-b]pyridine (0.024 g, 24% yield). 1H NMR (CDCl3, 400 MHz): δ 11.89 (s, 1H), 11.07 (s, 1H), 8.57 (d, J=2.1 Hz, 1H), 8.45 (d, J=2.4 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.92 (d, J=1.6 Hz, 1H), 7.89 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.46 (dd, J=1.8, 6.4 Hz, 2H)), 7.34 (d, J=2.4 Hz, 1H), 6.46 (s, 1H), 3.63 (s, 2H), 3.32 (s, 3H), 2.49-42 (m, 8H), 2.14 (s, 3H); MS ESI (m/z) 490 (M+1)+, calc. 489.53.

Workup

  1. customafter which it was partitioned between CH2Cl2 and 1 M NaOH
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in 3:2 MeOH
  6. additionacetone (5 mL), and 2 M NaOH (1.5 mL) was added
  7. stirringThe resulting mixture was stirred at 65° C. for 30 min
  8. customafter which it was partitioned between EtOAc and 1 M NaOH
  9. customThe organic layer was separated
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customto provide a residue that

Sources & evidence

ORD record
ord-f116c48a6c614cfdaf57fb484c6a0270
Source dataset
uspto-grants-2014_09
Patent number
US08846909B2

Reaction notes

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