Potassium Carbonate → HCID 9931699, compound

HRID 1978197Notes

Reaction equation

HRID 1978197 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:15]=[CH:14][N:13]([CH3:16])[N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[N:23]1[C:28]2[NH:29][C:30]3[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=3[NH:32][CH2:33][C:27]=2[CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:15]=[CH:14][N:13]([CH3:16])[N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([N:32]1[C:31]2[CH:34]=[CH:35][CH:36]=[CH:37][C:30]=2[NH:29][C:28]2[N:23]=[CH:24][CH:25]=[CH:26][C:27]=2[CH2:33]1)=[O:6]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 10889933HCID 10889933, compoundHCID 110307606,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

Product 1

HCID 9931699HCID 9931699, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Under anhydrous conditions a mixture of the 2-chloro-4-(1-methyl-1H-pyrazol-3-yl)-benzoic acid of Example 13, Step E (1.9 g, 8.05 mmol) and oxalyl chloride (0.79 mL, 9.0 mmol) in 20 mL of dichloromethane containing a catalytic amount of dimethylformamide was stirred at ambient temperature for 1 hour. The solvent was evaporated and the solid acid chloride was dissolved in 5 mL of dimethylformamide and added directly to a mixture of 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine of Example 1, Step B (1.59 g, 8.05 mmol) and potassium carbonate (1.25 g, 9.0 mmol). After stirring for 2 hours at ambient temperature the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over sodium sulfate, and concentrated to small volume. Flash chromatography of the residue (on silica Merck 60, ethyl acetate-hexane, gradient from 4:3 to 2:1) gave the product as a syrup which crystallized from diethyl ether (1.8 g, 61% yield1) as a white solid, m.p. 196-197° C. Another recrystallization from ethanol-diethyl ether provided a higher melting polymorph, m.p. 202° C. as determined by differential scanning calorimetry.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe solid acid chloride was dissolved in 5 mL of dimethylformamide
  3. stirringAfter stirring for 2 hours at ambient temperature the reaction mixture
  4. customwas partitioned between ethyl acetate and water
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to small volume

Sources & evidence

ORD record
ord-2a6144f0955a4155a30db765354255fd
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

Loading…