4'-Methoxy-(1,1'-biphenyl)-4-carboxaldehyde → N1-(isothiazolo[5,4-b]pyrazin-3-yl)-N3-((4'-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine

HRID 502573Notes

Reaction equation

HRID 502573 reaction equation
[S:1]1[C:5]2=[N:6][CH:7]=[CH:8][N:9]=[C:4]2[C:3]([NH:10][CH2:11][CH2:12][CH2:13][NH2:14])=[N:2]1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([CH:29]=O)=[CH:25][CH:24]=2)=[CH:19][CH:18]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[S:1]1[C:5]2=[N:6][CH:7]=[CH:8][N:9]=[C:4]2[C:3]([NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:29][C:26]2[CH:25]=[CH:24][C:23]([C:20]3[CH:21]=[CH:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=3)=[CH:28][CH:27]=2)=[N:2]1

Participants

6

Reactant 3

HCID 13944874'-Methoxy-(1,1'-biphenyl)-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58726848N1-(isothiazolo[5,4-b]pyrazin-3-yl)propane-1,3-diamine

Product 1

HCID 58726860N1-(isothiazolo[5,4-b]pyrazin-3-yl)-N3-((4'-methoxybiphenyl-4-yl)methyl)propane-1,3-diamineYield 12.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

N1-(Isothiazolo[5,4-b]pyrazin-3-yl)propane-1,3-diamine (410 mg, 1.96 mmol) and 4′-methoxybiphenyl-4-carbaldehyde (410 mg, 1.96 mmol) were combined in 1,2-dichloroethane (8 mL) and treated with sodium triacetoxyborohydride (506 mg, 2.35 mmol). The mixture was shaken at room temperature for 3 h. The reaction was diluted with methylene chloride, quenched with water and the layers were separated. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography, on silica gel, eluting with methylene chloride:methanol to yield N1-(isothiazolo[5,4-b]pyrazin-3-yl)-N3-((4′-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine (100 mg) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): 8.79 (d, 1H), 8.72 (d, 1H), 7.90 (t, 1H), 7.54 (m, 4H), 7.40 (d, 2H), 6.98 (d, 2H), 3.82 (s, 2H), 3.80 (s, 3H), 3.48 (t, 2H), 2.70 (m, 3H), 1.85 ppm (m, 2H). MW=405 confirmed by LC-MS, tr=9.59 min (Method Y) MH+=404-406.

Workup

  1. customquenched with water
  2. customthe layers were separated
  3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by flash column chromatography, on silica gel
  7. washeluting with methylene chloride

Sources & evidence

ORD record
ord-f4ed6acbf6114aef962dc4611c38e12a
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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