Dimethylformamide → HCID 44453591, compound

HRID 272711Notes

Reaction equation

HRID 272711 reaction equation
[OH:1][C:2]1[C:28]([O:29][CH3:30])=[CH:27][C:5]2[NH:6][C:7](=[O:26])[C:8]3[CH:14]=[CH:13][C:12]([C:15]4[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([O:24][CH3:25])[CH:16]=4)=[CH:11][C:9]=3[NH:10][C:4]=2[CH:3]=1.Br[CH2:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>C(OCC)(=O)C>[CH3:30][O:29][C:28]1[C:2]([O:1][CH2:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)=[CH:3][C:4]2[NH:10][C:9]3[CH:11]=[C:12]([C:15]4[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([O:24][CH3:25])[CH:16]=4)[CH:13]=[CH:14][C:8]=3[C:7](=[O:26])[NH:6][C:5]=2[CH:27]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 1419172-(Bromomethyl)tetrahydro-2H-pyranHCID 44453209HCID 44453209, compound

Product 1

HCID 44453591HCID 44453591, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of Example 476I (40 mg, 0.098 mmol), 2-bromomethyl-tetrahydro-2H-pyran (0.13 mL, 0.98 mmol), K2CO3 (136 mg, 0.98 mmol) and DMF (2 mL) was heated at 100° C. overnight, cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried (MgSO4), filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel with 49:1 dichloromethane/methanol to provide 23 mg (47%) of the desired product. MS (ESI) m/e 506 (M+H)+; 1H NMR (300 MHz, DMSO-d6) 9.66 (s, 1H), 8.01 (d, J=8.5 Hz, 1H), 7.77 (d, J=8.8 Hz, 1H), 7.71 (s, 1H), 7.53 (d, J=1.7 Hz, 1H), 7.35 (dd, J=1.7, 8.5 Hz, 1H), 7.26-7.31 (m, 2H), 6.69 (s, 1H), 6.64 (s, 1H), 4.03 (s, 3H), 3.72-3.94 (m, 3H), 3.67 (s, 3H), 3.60 (m, 1H), 3.39 (m, 1H), 1.82 (m, 1H), 1.64 (m, 1H), 1.41-1.55 (m, 3H), 1.27 (m, 1H).

Workup

  1. washwashed with water and brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by column chromatography on silica gel with 49:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-59744ac355e14de6b8f5f9e916ba941e
Source dataset
uspto-grants-2008_11
Patent number
US07456169B2

Reaction notes

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