Lithium Chloride → HCID 178461215, compound

HRID 81282Notes

Reaction equation

HRID 81282 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([O:43]C)[N:38]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Cl-].[Li+]>CC(N(C)C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:37]3[NH:38][C:39](=[O:43])[CH:40]=[CH:41][CH:42]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 178489657HCID 178489657, compound

Product 1

HCID 178461215HCID 178461215, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(5-chloropyridin-3-yl)-6-(6-methoxypyridin-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine (63.0 mg, 0.104 mmol), p-toluenesulfonic acid monohydrate (198 mg, 1.04 mmol), and lithium chloride (44.1 mg, 1.04 mmol) in DMA (1.0 mL) was heated at 100° C. for 24 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with water (10 mL). The reaction mixture was extracted with dichloromethane (3×10 mL). The combined organic layers were washed with water (2×10 mL), and brine (10 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. Purification of the residue on a silica gel column (0 to 10% CH2Cl2/MeOH) afforded 6-{4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridin-6-yl}pyridin-2(1H)-one. 1H NMR (400 MHz, CDCl3) δ 10.69 (br s, 1H), 8.71 (d, J=2.4 Hz, 1H), 8.50 (m, 1H), 8.02 (s, 1H), 7.86 (m, 1H), 7.50 (dd, J=9.0, 6.8 Hz, 1H), 7.32-7.41 (m, 2H), 7.23-7.31 (m, 3H), 6.79-6.86 (m, 1H), 6.58 (d, J=9.0 Hz, 1H), 4.66 (m, 1H), 4.08-4.14 (m, 2H), 3.92-4.07 (m, 2H), 3.62-3.74 (m, 1H), 3.36-3.54 (m, 3H), 1.39-1.51 (m, 2H), 1.02-1.18 (m, 1H), 0.80-0.94 (m, 1H), 0.75 (d, J=6.4 Hz, 3H), 0.55-0.71 (m, 4H), 0.36-0.52 (m, 2H). MS ES calc'd. for C34H35ClN6O2 [M+H]+ 595. found 595.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe reaction mixture was extracted with dichloromethane (3×10 mL)
  3. washThe combined organic layers were washed with water (2×10 mL), and brine (10 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue on a silica gel column (0 to 10% CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-52f912cc666b443e8d5cc8e192515de9
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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