Trifluoroacetic acid → 1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1H-benzo[d]imidazole

HRID 706439Notes

Reaction equation

HRID 706439 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH2:36][C:37]1[CH:38]=[N:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=1)[CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][C:14]([N:16]3[CH2:19][C:18]4([CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]4)[CH2:17]3)=[CH:15][C:10]=2[N:9]=[CH:8]1.FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH2:36][C:37]1[CH:38]=[N:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=1)[CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][C:14]([N:16]3[CH2:19][C:18]4([CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH2:17]3)=[CH:15][C:10]=2[N:9]=[CH:8]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118114062tert-butyl 2-(1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

Product 1

HCID 1180097831-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1H-benzo[d]imidazoleYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 2-(1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (0.53 g, 0.88 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (5.0 mL. 64.90 mmol). The reaction mixture was allowed to stir at room temperature. After 1 h, the mixture was concentrated, and the residue partitioned between 3 M ammonium hydroxide solution and dichloromethane. The phases were separated, and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Chromatographic purification (Combi-Flash, 40 g SiO2 gold column, 1-15% methanol/dichloromethane elute) afforded 0.28 g (64%) of the product as a solid: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J=2.1 Hz, 1H), 7.80 (s, 1H), 7.65 (dd, J=8.5, 2.4 Hz, 1H), 7.10 (d, J=8.6 Hz, 1H), 6.88-6.79 (m, 2H), 6.78-6.65 (m, 3H), 6.47 (dd, J=8.6, 2.1 Hz, 1H), 5.18 (s, 2H), 5.00 (s, 2H), 3.92 (s, 3H), 3.75 (s, 3H), 3.61 (s, 4H), 2.86-2.78 (m, 4H), 2.54 (b, 1H), 1.82-1.74 (m, 4H) ppm; (M+1)=500.

Workup

  1. concentrationthe mixture was concentrated
  2. customthe residue partitioned between 3 M ammonium hydroxide solution and dichloromethane
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with dichloromethane
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customChromatographic purification (Combi-Flash, 40 g SiO2 gold column, 1-15% methanol/dichloromethane elute)

Sources & evidence

ORD record
ord-afbb6bef823a4e8a8c6b87ab2dcb6f7a
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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