Formaldehyde → HCID 73330788, compound

HRID 517566Notes

Reaction equation

HRID 517566 reaction equation
[CH:1]([O-])=O.[CH3:4][N:5]1[C:9]([CH2:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([N:17]3[CH2:22][CH2:21][NH2+:20][CH2:19][CH2:18]3)[CH:12]=2)=[N:8][C:7]([C:23]2[O:27][N:26]=[C:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=3)[N:24]=2)=[N:6]1.C=O.[BH3-]C#N.[Na+]>CCO>[CH3:4][N:5]1[C:9]([CH2:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([N:17]3[CH2:22][CH2:21][N:20]([CH3:1])[CH2:19][CH2:18]3)[CH:12]=2)=[N:8][C:7]([C:23]2[O:27][N:26]=[C:25]([C:28]3[CH:29]=[CH:30][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:32][CH:33]=3)[N:24]=2)=[N:6]1

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 5003444Sodium cyanoborohydrideHCID 86711506HCID 86711506, compound

Product 1

HCID 73330788HCID 73330788, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of 4-(4-((1-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-5-yl)methyl)pyridin-2-yl)piperazin-1-ium formate (100 mg, 0.2 mmol) in EtOH (1 mL), formaldehyde (0.5 mL, 6.0 mmol, 38% in H2O) and paraformaldehyde (100 mg, 3.3 mmol) in EtOH (1 mL) was stirred at RT, then treated with NaBH3CN (63 mg, 1.0 mmol) in one portion. The mixture was stirred at RT for 1 h, and then concentrated to give the crude product, which was purified by pre-HPLC (Mobile phase: A=10 mM NH4HCO3/H2O, B=MeCN; Gradient: B=60%-95% in 18 min; Column: XBridge (C18, 5 um, 30 mm*150 mm) to afford 5-(1-methyl-5-((2-(4-methyl piperazin-1-yl)pyridin-4-yl)methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole as a white solid (50 mg, 50%). MS (ES+) C23H23F3N8O2 requires: 500, found: 501[M+H]+; 1H NMR (500 MHz, DMSO-d6) δ ppm 8.28 (bs, 1H), 8.22 (d, J=7.0 Hz, 2H), 8.05 (d, J=5.0 Hz, 1H), 7.60 (d, J=8.0 Hz, 2H), 6.80 (s, 1H), 6.55 (d, J=5.0 Hz, 1H), 4.25 (s, 2H), 4.00 (s, 3H), 3.47 (t, J=4.8 Hz, 4H), 2.50 (t, J=5.3 Hz, 4H), 2.21 (s, 3H).

Workup

  1. concentrationconcentrated
  2. customto give the crude product, which
  3. customwas purified by pre-HPLC (Mobile phase
  4. waitGradient: B=60%-95% in 18 min

Sources & evidence

ORD record
ord-d0553bd45c1f4acfb7661220ab90cc73
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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