Methanol → HCID 178504974, compound

HRID 81254Notes

Reaction equation

HRID 81254 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]([NH2:37])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:38][S:39](Cl)(=[O:41])=[O:40].CO.[Li+].[OH-]>ClCCl.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:35][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]([NH:37][S:39]([CH3:38])(=[O:41])=[O:40])[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 31297Methanesulfonyl chlorideHCID 178461227HCID 178461227, compound

Product 1

HCID 178504974HCID 178504974, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridin-6-amine (70 mg, 0.13 mmol) in dichloromethane (2.0 mL) was added TEA (27 mg, 0.27 mmol) at 0° C. followed by slow addition of methane sulfonyl chloride (15 mg, 0.13 mmol). The reaction was warmed slowly to room temperature and stirred for 2 h. The reaction was then diluted with CH2Cl2 (70 mL) and water (10 mL). The organic layer was separated, washed with saturated brine solution (2×20 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was dissolved in THF (1 mL), MeOH (1 mL), and H2O (0.5 mL), and then LiOH (20 mg, 0.48 mmol) was added. The reaction was stirred at room temperature for 1 h. The reaction was then concentrated under reduced pressure. The residue was purified by silica gel chromatography (90% EtOAc/petroleum ether). The isolated product was further purified by preparative HPLC (acetonitrile:water: 0.1% v/v trifluoroacetic acid modifier) to afford N-{4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridin-6-yl}methanesulfonamide (TFA salt). MS ES/APCl calc'd. for C30H36ClN6O3S[M+H]+ 595. found 595. 1H NMR (400 MHz, DMSO-d6): δ 10.26 (bs, 1H), 8.77 (d, J=2.0 Hz, 2H), 8.23 (t, J=2.0 Hz, 1H), 7.43 (d, J=7.2 Hz, 2H), 7.29-7.21 (m, 3H), 6.99 (s, 1H), 4.75 (t, J=5.2 Hz, 1H), 3.92-3.88 (m, 4H), 3.75-3.70 (m, 1H), 3.54-3.49 (m, 2H), 3.26 (s, 3H), 3.25-3.20 (m, 1H), 1.41-1.35 (m, 2H), 1.08-1.07 (m, 1H), 0.76-0.74 (m, 3H), 0.70 (d, J=6.8 Hz, 3H), 0.58-0.55 (m, 1H), 0.50-0.47 (m, 1H), 0.40-0.27 (m, 2H).

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated brine solution (2×20 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in THF (1 mL)
  7. stirringThe reaction was stirred at room temperature for 1 h
  8. concentrationThe reaction was then concentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (90% EtOAc/petroleum ether)
  10. customThe isolated product was further purified by preparative HPLC (acetonitrile:water: 0.1% v/v trifluoroacetic acid modifier)

Sources & evidence

ORD record
ord-d50d6c3a3b0c4e7eb0bef8b1e6f7a506
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

Loading…