Sodium hydride → tert-Butyl 4-[(6-{[2-(4-chlorophenyl)-7-oxothieno[2,3-d]pyridazin-6(7H)-yl]methyl}pyridin-2-yl)oxy]piperidine-1-carboxylate

HRID 2239363Notes

Reaction equation

HRID 2239363 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[NH:13][N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].CS(O[CH2:25][C:26]1[N:31]=[C:30]([O:32][CH:33]2[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]2)[CH:29]=[CH:28][CH:27]=1)(=O)=O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[N:13]([CH2:25][C:26]4[N:31]=[C:30]([O:32][CH:33]5[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:37][CH2:38]5)[CH:29]=[CH:28][CH:27]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 115798042-(4-Chlorophenyl)thieno[2,3-d]pyridazin-7(6H)-oneHCID 86618691tert-Butyl 4-[(6-{[(methylsulfonyl)oxy]methyl}pyridin-2-yl)oxy]piperidine-1-carboxylate2×

Product 1

HCID 68711796tert-Butyl 4-[(6-{[2-(4-chlorophenyl)-7-oxothieno[2,3-d]pyridazin-6(7H)-yl]methyl}pyridin-2-yl)oxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 2-(4-chlorophenyl)thieno[2,3-d]pyridazin-7(6H)-one (0.32 g, 1.22 mmol) in DMF (10 mL) was added 60% sodium hydride in oil (0.06 g, 1.34 mmol, 55%). Stirred for 10 minutes under N2 atmosphere before addition of tert-butyl 4-[(6-{[(methylsulfonyl)oxy]methyl}pyridin-2-yl)oxy]piperidine-1-carboxylate (crude product from step d) dissolved in DMF (10 mL). The resulting mixture was stirred for 18 hours at room temperature followed by prep-HPLC purification to give the product. Yield: 0.22 g (32% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.60-7.64 (m, 2H), 7.40-7.51 (m, 4H), 6.75 (d, 1H, J=7.28 Hz), 6.54 (d, 1H, J=8.24 Hz), 5.47 (s, 2H), 4.90-4.99 (m, 1H), 3.58-3.70 (m, 2H), 2.94-3.04 (m, 2H), 1.73-1.82 (m, 2H), 1.47-1.60 (m, 2H), 1.39 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 162.9, 157.3, 155.1, 153.7, 152.5, 140.3, 139.5, 136.4, 136.1, 133.1, 131.2, 129.8, 128.3, 118.9, 114.2, 110.3, 79.7, 70.6, 55.7, 41.3, 30.8, 28.7.

Workup

  1. customfollowed by prep-HPLC purification
  2. customto give the product

Sources & evidence

ORD record
ord-ef758a58c44f4993ab2938ffa0a40eaf
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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