3,4-dihydro-2H-pyran → tetrahydro-pyran-2-yl-1H-pyrazole-3-carboxylic acid [4-(tetrahydro-pyran-2-yloxy)-cyclohexyl]-amide

HRID 1169904Notes

Reaction equation

HRID 1169904 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]2[C:15]([N+]([O-])=O)=[CH:14][NH:13][N:12]=2)=[O:10])[CH2:4][CH2:3]1.[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH2:38]1>C(Cl)Cl.C(Cl)(Cl)Cl.C1COCC1>[O:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]1[O:1][CH:2]1[CH2:3][CH2:4][CH:5]([NH:8][C:9]([C:11]2[CH:15]=[CH:14][N:13]([CH:38]3[CH2:39][CH2:40][CH2:41][CH2:42][O:37]3)[N:12]=2)=[O:10])[CH2:6][CH2:7]1

Participants

8

Reactant 4

HCID 80803,4-dihydro-2H-pyranHCID 186148PyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178522231HCID 178522231, compound

Product 1

HCID 131726921tetrahydro-pyran-2-yl-1H-pyrazole-3-carboxylic acid [4-(tetrahydro-pyran-2-yloxy)-cyclohexyl]-amide

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-nitro-1H-pyrazole-3-carboxylic acid 4-hydroxy-cyclohexylamide (1.95 g; 7.67 mmol) in a mix of THF (50 ml) and chloroform (100 ml), was treated with 3,4-dihydro-2H-pyran (1.54 ml, 15.34 mmol) and p-toluenesulphonic acid monohydrate (100 mg). The reaction mixture was stirred at room temperature overnight, and then excess pyran (0.9 ml) was added in total to bring reaction to completion. The reaction mixture was diluted with CH2Cl2 and washed successively with saturated aqueous sodium bicarbonate, water and brine. The resulting solution was reduced in vacuo and subject to Biotage column chromatography, eluting with hexane (2 column lengths) followed by 30% ethyl acetate:hexane (10 column lengths), 70% ethyl acetate:hexane (10 column lengths) to give 1.25 g of 4-nitro-1-(tetrahydro-pyran-2-yl-1H-pyrazole-3-carboxylic acid [4-(tetrahydro-pyran-2-yloxy)-cyclohexyl]-amide. (LC/MS: Rt 2.97, [M+H]+ 423).

Workup

  1. customreaction to completion
  2. washwashed successively with saturated aqueous sodium bicarbonate, water and brine
  3. washeluting with hexane (2 column lengths)

Sources & evidence

ORD record
ord-ab6b42719f064b9fb895687014c28fc8
Source dataset
uspto-grants-2010_11
Patent number
US07825140B2

Reaction notes

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