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

HRID 502596Notes

Reaction equation

HRID 502596 reaction equation
[S:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH: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+]>C(O)(=O)C.C(Cl)Cl>[S:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH: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 58727204N1-(isothiazolo[5,4-b]pyridin-3-yl)propane-1,3-diamine

Product 1

HCID 58726876N1-(isothiazolo[5,4-b]pyridin-3-yl)-N3-((4'-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of N1-(isothiazolo[5,4-b]pyridin-3-yl)propane-1,3-diamine (1.20 g, 5.77 mmol), 4′-methoxybiphenyl-4-carbaldehyde (1.22 g, 5.77 mmol), sodium triacetoxyborohydride (2.50 g, 11.8 mmol) and acetic acid (one drop) was taken up in methylene chloride (25 mL) and stirred overnight at room temperature under argon. The crude reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate and washed successively with saturated aqueous sodium bicarbonate solution and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with 95:5 methylene chloride:methanol yielded N1-(isothiazolo[5,4-b]pyridin-3-yl)-N3-((4′-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine. 1H NMR (300 MHz, CD3OD): 8.66-8.68 (d, 1H), 8.40-8.45 (d, 1H), 7.33-7.45 (m, 7H), 6.96 (s, 1H), 6.93 (s, 3.83 (s, 2H), 3.80 (s, 3H), 3.58-3.63 (t, 2H), 2.78-2.83 (t, 2H), 1.96-2.00 ppm (t, 2H). MW=405 confirmed by LC-MS, tr=9.08 min (Method Y) MH+=406.

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. additiondiluted with ethyl acetate
  4. washwashed successively with saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by column chromatography
  9. washon silica gel, eluting with 95:5 methylene chloride

Sources & evidence

ORD record
ord-3f6697008f3c4ff2869be6b1fd0ce28d
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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