Hydrochloric Acid → Lcq908

HRID 76056Notes

Reaction equation

HRID 76056 reaction equation
C[O:2][C:3](=[O:34])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]4[CH:25]=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=4)=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[Li+].[OH-].Cl>C1COCC1>[F:33][C:30]([F:31])([F:32])[C:27]1[N:26]=[CH:25][C:24]([NH:23][C:20]2[CH:21]=[CH:22][C:17]([C:14]3[CH:15]=[CH:16][C:11]([CH:8]4[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:34])=[O:2])[CH2:10][CH2:9]4)=[CH:12][CH:13]=3)=[N:18][CH:19]=2)=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 24938267Methyl 2-((1r,4r)-4-(4-(5-((6-(trifluoromethyl)pyridin-3-yl)amino)pyridin-2-yl)phenyl)cyclohexyl)acetate

Product 1

HCID 53387035Lcq908

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A THF solution of (4-{4-[5-(6-trifluoromethyl-pyridin-3-ylamino)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester was treated with 10% aqueous LiOH and heated to 50° C. overnight. Upon reaction completion, the mixture was acidified with concentrated HCl. The resulting precipitate was isolated by filtration to afford the title compound: 1H NMR (400 MHz, DMSO-d6) δ 1.08-1.19 (m, 1H) 1.14 (dd, J=12.63, 2.27 Hz, 1H) 1.44-1.56 (m, 1H) 1.50 (dd, J=12.51, 2.65 Hz, 1H) 1.75 (br. S., 1H) 1.84 (d, J=10.61 Hz, 4H) 2.14 (d, J=6.82 Hz, 2H) 2.54 (m, 1H) 7.33 (d, J=8:34 Hz, 2H) 7.65 (d, J=2.53 Hz, 1H) 7.68-7.74 (m, 1H) 7.70 (d, J=8.34 Hz, 1H) 7.89 (d, J=8.59 Hz, 1H) 7.95 (d, J=8.59 Hz, 2H) 8.46 (d, J=2.78 Hz, 1H) 8.54 (d, J=2.53 Hz, 1H) 9.20 (s, 1H); (M+H)+456.3. Alternatively, the methyl ester can be dissolved in a mixture of THF and water, and treated with aqueous sodium hydroxide (4 equiv). The mixture can then be stirred at 50 degrees for 12 hours, at which point the THF is removed under reduced pressure to yield an opaque, white slurry, which affords the title compound as the corresponding sodium salt upon filtration. 1H NMR (DMSO-d6, 500 MHz) δ 10.05 (s, 1H), 8.59 (d, 1H, J=2.8 Hz), 8.54 (s, 1H), 7.92 (d, 2H, J=8.2 Hz), 7.86 (d, 1H, J=8.8 Hz), 7.75 (dd, 1H, J=8.7.2.7 Hz), 7.69 (s, 2H), 7.27 (d, 2H, J=8.5 Hz), 2.45 (m, 1H), 1.84 (m, 4H), 1.67-1.80 (m, 3H), 1.41 (m, 2H), 1.02 (m, 2H); MS m/z 456 (M-Na+2H)+.

Workup

  1. customUpon reaction completion
  2. customThe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-c975ada4302a4d3aab1808307125b0e4
Source dataset
uspto-grants-2014_09
Patent number
US08835451B2

Reaction notes

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