Sodium hydride → 2-butyl-3-(2'-(N-triphenylmethyltetrazol-5-yl)biphen-4-yl)methyl-1H-imidazo[4,5-b]pyridine

HRID 1729395Notes

Reaction equation

HRID 1729395 reaction equation
[H-].[Na+].[CH2:3]([C:7]1[NH:8][C:9]2[C:10]([N:15]=1)=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:5][CH3:6].[C:16]1([C:22]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:23]2[C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]3[CH:39]=[CH:38][C:37]([CH2:40]Br)=[CH:36][CH:35]=3)=[N:26][N:25]=[N:24]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C)C=O>[CH2:3]([CH:7]1[N:15]([CH2:40][C:37]2[CH:36]=[CH:35][C:34]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[C:27]3[N:23]([C:22]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[N:24]=[N:25][N:26]=3)=[CH:39][CH:38]=2)[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[NH:8]1)[CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 124677102-butyl-1H-imidazo[4,5-b]pyridine

Product 1

HCID 1317172412-butyl-3-(2'-(N-triphenylmethyltetrazol-5-yl)biphen-4-yl)methyl-1H-imidazo[4,5-b]pyridineYield 23.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of NaH (102 mg of an 807. dispersion, 3.39 mmol) in dry dimethylformamide (6 mL) at rt was added 2-butylimidazo[4,5-b]pyridine (495 rag, 2.83 mmol) in one portion. After 20 minutes, the mixture was cooled to 0° C. and N-triphenylmethyl-5-(4'-bromomethylbiphenyl-2-yl)-tetrazole (1.50 g, 2.70 mmol) was added in one portion. The resulting dark colored mixture was warmed to rt and stirred for 15 hours. The excess Nail was quenched with water (1 mL) and the bulk of the DMF was removed in vacuo at 40°-50° C. Extraction with EtOAc (4×20 mL) from brine (60 mL), drying (K2CO3), and concentration gave a thick dark oil. Purification by flash chromatography (SiO2, solvent gradient: 80% EtOAc/hexanes, 100% EtOAc) gave 417 mg (23%) of 2-butyl-3-(2'-(N-triphenylmethyltetrazol-5-yl)biphen-4-yl)methyl-1H-imidazo[ 4,5-b ]pyridine as a thick oil: Rf=0.75 (SiO2, 100% EtOAc), 1H NMR (300 MHz, CDCl3) δ 8.35 (1H, dd, J=6, 1 Hz), 8.05 (1H, dd, J=9, 1 Hz), 7.92 (1H, dd, J=9, 1.5 Hz), 7.51-7.42 (3H, m), 7.36-7.20 (11 H, M), 7.07 (2H, d, 7 Hz), 6.96-6.89 (7H, m), 5.40 (2H, s), 2.73 (2H, t, J=7.5 Hz), 1.84-1.70 (2H, m), 1.41-1.30 (2H, m), 0.88 (3H, t, J=7.5 Hz).

Workup

  1. temperatureThe resulting dark colored mixture was warmed to rt
  2. customThe excess Nail was quenched with water (1 mL)
  3. customthe bulk of the DMF was removed in vacuo at 40°-50° C
  4. extractionExtraction with EtOAc (4×20 mL) from brine (60 mL)
  5. customdrying
  6. concentration(K2CO3), and concentration
  7. customgave a thick dark oil
  8. customPurification by flash chromatography (SiO2, solvent gradient: 80% EtOAc/hexanes, 100% EtOAc)

Sources & evidence

ORD record
ord-ed4c1d51e58548b3b869117caecc1d14
Source dataset
uspto-grants-1994_07
Patent number
US05332744

Reaction notes

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