Cesium carbonate → HCID 59410233, compound

HRID 1891368Notes

Reaction equation

HRID 1891368 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([S:9]([N:12]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]3[CH:19]=[CH:20][CH:21]=[CH:22][C:13]2=3)(=[O:11])=[O:10])=[CH:4][C:3]=1[C:23]1[C:24]([CH3:31])=[CH:25][C:26]([C:29]#[N:30])=[N:27][CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:39][CH2:40][CH2:41][OH:42]>C(#N)C>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:39][CH2:40][CH2:41][OH:42])[C:5]([S:9]([N:12]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]3[CH:19]=[CH:20][CH:21]=[CH:22][C:13]2=3)(=[O:10])=[O:11])=[CH:4][C:3]=1[C:23]1[C:24]([CH3:31])=[CH:25][C:26]([C:29]#[N:30])=[N:27][CH:28]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 123083-Bromo-1-propanolHCID 59410232HCID 59410232, compound

Product 1

HCID 59410233HCID 59410233, compoundYield 60.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

To 5-[2-chloro-4-hydroxy-5-(2,3,4,5-tetrahydro-benzo[b]azepine-1-sulfonyl)-phenyl]-4-methyl-pyridine-2-carbonitrile (90 mg, 0.2 mmol) in dry acetonitrile (1.5 mL), was added Cs2CO3 (130 mg, 0.4 mmol), followed by an addition of 3-bromo-1-propanol (36 mg, 0.26 mmol). The mixture was heated at 45° C. for 24 hrs and partitioned between ethyl acetate (10 mL) and water (5 mL). The organic layer was separated, washed with brine (2×5 mL) and dried over MgSO4. After filtration, the mixture was concentrated and purified by TLC plates eluting with ethyl acetate in hexanes (1/1) to give 5-[2-chloro-4-(3-hydroxy-propoxy)-5-(2,3,4,5-tetrahydro-benzo[b]azepine-1-sulfonyl)-phenyl]-4-methyl-pyridine-2-carbonitrile 9-1 as a white solid (62 mg). MS: 511.9 (M+H)+; tR=8.07 min (method 2). NMR (CDCl3), δ, 8.344 (1H, s), 7.634 (1H, s), 7.597 (1H, s), 7.235 (1H, s), 7.164-7.184 (2H, m), 7.008-7.060 (1H, m), 6.871 (1H, d, J=7.8 Hz), 4.287 (2H, t), 3.769-3.805 (4H, m), 2.775-2.786 (2H, m), 2.064 (3H, s), 1.850-1.905 (2H, m), 1.959-1.995 (2H, m), 1.653 (2H, s).

Workup

  1. custompartitioned between ethyl acetate (10 mL) and water (5 mL)
  2. customThe organic layer was separated
  3. washwashed with brine (2×5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationAfter filtration
  6. concentrationthe mixture was concentrated
  7. custompurified by TLC plates
  8. washeluting with ethyl acetate in hexanes (1/1)

Sources & evidence

ORD record
ord-ddc83c70ee7d4a4190258f06e0e1a7ac
Source dataset
uspto-grants-2013_08
Patent number
US08507536B2

Reaction notes

Loading…