Sodium hydride → HCID 57501780, compound

HRID 601544Notes

Reaction equation

HRID 601544 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:26])[N:12]([C:17]4[CH:18]=[C:19]5[C:23](=[CH:24][CH:25]=4)[NH:22][CH:21]=[CH:20]5)[CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br.Br[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:26])[N:12]([C:17]4[CH:18]=[C:19]5[C:23](=[CH:24][CH:25]=4)[N:22]([CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH:21]=[CH:20]5)[CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 57501776HCID 57501776, compound

Product 1

HCID 57501780HCID 57501780, compoundYield 52.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 2-(4-chloro-phenyl)-5-(1H-indol-5-yl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (49 mg, 0.13 mmol) in DMF (1 mL) and add sodium hydride (17 mg, 0.42 mmol). Stir the mixture at room temperature for 30 min then add 2-bromomethyl-pyridine hydrobromide (35 mg, 0.14 mmol). Stir the mixture at room temperature for 5 h, then dilute with EtOAc (30 mL) and wash with saturated NaHCO3 (10 mL). Dry, filter and concentrate the organic solution. Purify the crude material by flash chromatography, using a linear gradient of 20% to 80% EtOAc/hexanes as eluent, to give the title compound (32 mg, 52%). MS (ES+) 471.0 (M+1)+. 1H NMR (400 MHz, CDCl3) δ: 8.55-8.53 (m, 1H), 8.05 (d, 2H, J=8.4 Hz), 7.73 (dt, 1H, J=7.7, 1.8 Hz), 7.62 (d, 2H, J=8.8 Hz), 7.57-7.55 (m, 2H), 7.45 (d, 1H, J=8.8 Hz), 7.30-7.26 (m, 1H), 7.10 (dd, 1H, J=8.6, 2.0 Hz), 7.03 (d, 1H, J=7.9 Hz), 6.52 (d, 1H, J=3.5 Hz), 5.53 (s, 2H), 4.10 (t, 2H, J=7.0 Hz), 3.27 (t, 2H, J=7.0 Hz).

Workup

  1. stirringStir the mixture at room temperature for 5 h
  2. washwash with saturated NaHCO3 (10 mL)
  3. customDry
  4. filtrationfilter
  5. concentrationconcentrate the organic solution
  6. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-7e45d47747764a7daec1c2401bb6bbfc
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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