Trifluoroacetic acid → [3-Butyl-6,7-dihydro-5-[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]imidazo[1,5-a]pyridin-8(5H)-ylidene]acetic acid

HRID 22046Notes

Reaction equation

HRID 22046 reaction equation
[CH2:1]([C:5]1[N:9]2[CH:10]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:34]4[NH:38][N:37]=[N:36][N:35]=4)=[CH:24][CH:23]=3)[CH2:11][CH2:12][C:13](=[CH:14][C:15]([O:17]C(C)(C)C)=[O:16])[C:8]2=[CH:7][N:6]=1)[CH2:2][CH2:3][CH3:4].C(O)(C(F)(F)F)=O>>[CH2:1]([C:5]1[N:9]2[CH:10]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:34]4[NH:38][N:37]=[N:36][N:35]=4)=[CH:24][CH:23]=3)[CH2:11][CH2:12][C:13](=[CH:14][C:15]([OH:17])=[O:16])[C:8]2=[CH:7][N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178441592HCID 178441592, compound

Product 1

HCID 178441590[3-Butyl-6,7-dihydro-5-[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]imidazo[1,5-a]pyridin-8(5H)-ylidene]acetic acidYield 96%

Procedure

To a solution of 32 mg (0.0627 mmol) of tert-butyl ester (the title compound of Example 15) in 2 mL of CDCl3 at room temperature was added 0.5 mL of TFA, and the progress of the reaction was monitored by 1H NMR. The resulting yellow solution was stirred at room temperature for 1 h and concentrated in vacuo. The crude product was dissolved in a minimum amount of methanol, diluted with methylene chloride, then triturated with ether and hexane at 5° C. to give 27 mg (96%) of the title compound of Example 16 as a solid: mp 154.0°-155.5° C. (decomposed); 1H NMR (CD3OD) δ 0.84 (t, J=7.5 Hz, 3H), 1.2-1.45 (m, 2H), 1.45-1.63 (m, 2H), 2.25-2.55 (m, 3H), 2.60-2.9 (m, 2H), 3.52-3.7 (m, 1H), 5.95 (br s, 1 H), 6.59 (s, 1H), 6.99 (d, J=7.5 Hz, 2H), 7.19 (d, J=7.7 Hz, 2H), 7.50-7.62 (m, 2H, 7.67 (d, J=7.2 Hz, 2H), 8.16 (s, 1H); HRMS. calcd for M+H: 455.2195. Found: 455.2195.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe crude product was dissolved in a minimum amount of methanol
  3. additiondiluted with methylene chloride
  4. customtriturated with ether and hexane at 5° C.

Sources & evidence

ORD record
ord-42901f26d2324dcd8f258d6688626506
Source dataset
uspto-grants-1995_06
Patent number
US05426105

Reaction notes

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