Ozone → 4-[2-(4-tert-Butyl-phenyl)-3H-imidazo[4,5-c]pyridin-7-yl]-piperazine-1-carboxylic acid benzyl ester

HRID 729355Notes

Reaction equation

HRID 729355 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]=[CH:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=[O+][O-].P(OCC)(OCC)OCC.[C:29]([C:33]1[CH:38]=[CH:37][C:36]([C:39]2[NH:40][C:41]3[C:46]([NH2:47])=[CH:45][N:44]=[CH:43][C:42]=3[N:48]=2)=[CH:35][CH:34]=1)([CH3:32])([CH3:31])[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][N:47]([C:46]2[C:41]3[N:40]=[C:39]([C:36]4[CH:37]=[CH:38][C:33]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:34][CH:35]=4)[NH:48][C:42]=3[CH:43]=[N:44][CH:45]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 24823OzoneHCID 31215Triethyl phosphiteHCID 643471Benzyl 3-pyrroline-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 178440764HCID 178440764, compound

Product 1

HCID 578327604-[2-(4-tert-Butyl-phenyl)-3H-imidazo[4,5-c]pyridin-7-yl]-piperazine-1-carboxylic acid benzyl esterYield 2.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

2,5-Dihydro-pyrrole-1-carboxylic acid benzyl ester 6 was dissolved in DCM (5 ml) and MeOH (2 ml). It was cooled to −78° C. and treated with ozone until it was blue in color. Triethyl phosphite (246 mg, 1.48 mmol) was added and the solution was allowed to stir for 5 minutes. 2-(4-tert-Butyl-phenyl)-1H-imidazo[4,5-c] pyridin-7-ylamine 4 (266 mg, 1.00 mmol) was added followed by sodium triacetoxyborohydride (538 mg, 2.54 mmol). This mixture was allowed to stir for 18 hours. Mass spectroscopy showed no starting material left after this time, and the solvent was removed under vacuum. The crude was taken up in ethyl acetate and washed with a saturated sodium bicarbonate solution, brine, dried over MgSO4, and the crude was purified by HPLC (Method E), yielding the title product 7 (12 mg (2.5%), 0.026 mmol). 1H NMR (DMSO-d6): δ 8.88 (bs, 1H), 8.23 (d, J=8.5 Hz, 2H), 7.96 (s, 1H), 7.68 (d, J=8.5 Hz, 2H), 7.38 (m, 5H), 5.15 (s, 2H), 1.33 (s, 9H). MS (ESI-POS): [M+H]+=470; MS(ESI-NEG):[M−H]−=468.

Workup

  1. stirringto stir for 18 hours
  2. waitleft after this time
  3. customthe solvent was removed under vacuum
  4. washwashed with a saturated sodium bicarbonate solution, brine
  5. dry with materialdried over MgSO4
  6. customthe crude was purified by HPLC (Method E)

Sources & evidence

ORD record
ord-ad390ac47f0c4b5e9dc6f68d48e90946
Source dataset
uspto-grants-2009_09
Patent number
US07582634B2

Reaction notes

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