Potassium Carbonate → HCID 58204514, compound

HRID 1498431Notes

Reaction equation

HRID 1498431 reaction equation
Cl.[OH:2][CH2:3][CH2:4][N:5]([CH:28]([CH3:30])[CH3:29])[C:6]([C:8]1[N:17]=[C:16]2[N:10]([CH2:11][CH2:12][O:13][C:14]3[CH:21]=[C:20]([CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[CH:19]=[CH:18][C:15]=32)[CH:9]=1)=[O:7].C(=O)([O-])[O-].[K+].[K+].[CH3:37][N:38]([CH3:43])[C:39](=[O:42])[CH2:40]Cl>CN(C=O)C>[CH3:37][N:38]([CH3:43])[C:39](=[O:42])[CH2:40][N:25]1[CH2:26][CH2:27][CH:22]([C:20]2[CH:19]=[CH:18][C:15]3[C:16]4[N:10]([CH:9]=[C:8]([C:6]([N:5]([CH2:4][CH2:3][OH:2])[CH:28]([CH3:30])[CH3:29])=[O:7])[N:17]=4)[CH2:11][CH2:12][O:13][C:14]=3[CH:21]=2)[CH2:23][CH2:24]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 67050777HCID 67050777, compound

Product 1

HCID 58204514HCID 58204514, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid (2-hydroxy-ethyl)-isopropyl-amide hydrochloride (127 mg, 0.23 mmol) in DMF (2 mL) was added potassium carbonate (127 mg, 0.92 mmol), N,N-dimethyl-2-chloroacetamide (36 mg, 0.3 mmol) and KI (catalytic) and stirring continued at RT for 72 h before concentrating in vacuo. The resultant residue was diluted with ethyl acetate and washed with water followed by brine, then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was passed down an Isolute SCX-2 cartridge eluting with DCM/methanol then 2M NH3 in methanol. Basic fractions were combined and concentrated in vacuo, the residue subjected to RPHPLC (C18 column, gradient 5 to 95% CH3CN in water+0.1% HCO2H) to give 356 as a colourless glass (22 mg, 20%). LCMS: RT=1.90 min, [M+H]+=484 1H NMR 400 MHz (CDCl3) δ: 8.42 (2 H, s), 8.20 (1 H, br, s), 8.34 (1 H, d, J=8.32 Hz), 7.81 (1 H, s), 7.04 (1 H, dd, J=8.40, 1.77 Hz), 6.90 (1 H, d, J=1.69 Hz), 4.63 (2 H, m), 4.45-4.44 (4 H, m), 3.38 (3 H, m), 3.32 (2 H, m), 3.16 (2 H, d, J=11.21 Hz), 3.11 (3 H, s), 2.99 (3 H, s), 2.56 (1 H, m), 2.48 (2 H, m), 1.87 (4 H, m), 1.42 (6 H, d, J=6.46 Hz)

Workup

  1. concentrationbefore concentrating in vacuo
  2. additionThe resultant residue was diluted with ethyl acetate
  3. washwashed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washeluting with DCM/methanol
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-239c9ad549aa48d0bee68a1fc459630a
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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