Triethylamine → [2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(2,3-dihydro-benzo[1,4]oxazin-4-yl)-methanone

HRID 1877356Notes

Reaction equation

HRID 1877356 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[N:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.[O:19]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][CH2:21][CH2:20]1.C(N(CC)CC)C.[I-].ClC1C=CC=C[N+]=1C>ClCCl>[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[C:6]([C:7]([N:22]2[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:19][CH2:20][CH2:21]2)=[O:9])=[CH:10][CH:11]=[CH:12][N:13]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 5850963,4-Dihydro-2H-1,4-benzoxazineHCID 167959962-(2,5-Dichloro-phenoxy)-nicotinic acid

Product 1

HCID 59294483[2-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(2,3-dihydro-benzo[1,4]oxazin-4-yl)-methanoneYield 18.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (42.6 mg, 0.15 mmol, 1.0 equiv; Example 31, Step 1) in dichloromethane (1.5 mL) was added 3,4-dihydro-2H-benzo[1,4]oxazine (22.9 mg, 0.17 mmol, 1.1 equiv; [CAS RN 5735-53-5]), triethylamine (30.4 mg, 42 μL, 0.3 mmol, 2.0 equiv; [CAS RN 121-44-8]) and 2-chloro-1-methylpyridinium iodide (42.2 mg, 0.17 mmol, 1.1 equiv; [CAS RN 14338-32-0]). The reaction mixture was stirred at rt over night. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 11 mg (18%) of the title compound. MS (ISP): 401.0 [M+H]+.

Workup

  1. customRemoval of the solvent mixture
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-088ecb34b69c4381ac6ae2aa185d75b2
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

Loading…