Hydrochloric Acid → HCID 178482118, compound

HRID 81199Notes

Reaction equation

HRID 81199 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:31][CH2:30][C@H:29]([CH3:32])[CH2:28][CH2:27]4)[C:15]([N:17]([CH3:24])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:16][C:12]=3[CH:11]=[C:10](C3NC(=O)ON=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[OH-:39].[Na+].Cl.[CH3:42][OH:43]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:27][CH2:28][C@H:29]([CH3:32])[CH2:30][CH2:31]4)[C:15]([N:17]([CH3:24])[C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:42]([OH:43])=[O:39])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 178482116HCID 178482116, compound

Product 1

HCID 178482118HCID 178482118, compound

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[methyl(phenyl)amino]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 3.174 step 2, 160 mg, 0.339 mmol) in methanol (2 mL) in a sealable tube was added 30% sodium hydroxide solution (4 mL). The tube was sealed and heated to 80° C. for 14 hours. The reaction mixture was cooled to room temperature and neutralized with the addition of 1.5 M HCl solution. The solution was extracted with ethyl acetate (4×25 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative HPLC (Kromasil C18, water/acetonitrile+0.1% TFA modifier) to afford 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[methyl(phenyl)amino]-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (TFA salt). MS ES/APCl calc'd. for C27H28ClN6O2 [M+H]+ 490. found 490. 1H NMR (400 MHz, DMSO-d6): δ 12.79 (bs, 1H), 8.78 (d, J=12.8 Hz, 2H), 8.30 (s, 1H), 7.82 (s, 1H), 7.26 (t, J=7.6 Hz, 2H), 6.96-6.87 (m, 3H), 3.40-3.30 (m, 2H), 3.21 (s, 3H), 1.46-1.42 (m, 2H), 1.26-1.01 (m, 4H), 0.86-0.84 (m, 3H), 0.73-0.71 (m, 4H). The compounds in Table 3 were prepared as described above or using procedures which were analogous to those described above. In some cases, enantiomers or diastereomers were separated by chromatography on chiral columns using standard techniques. Amines used to displace the bromide of Preparative Example 3.1 are described above, commercially available, known in the literature, or can be prepared using methods readily available in the literature.

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionThe solution was extracted with ethyl acetate (4×25 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (Kromasil C18, water/acetonitrile+0.1% TFA modifier)

Sources & evidence

ORD record
ord-24529248f81a43b7966e16417a9cc92d
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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