Pyridine → HCID 66784763, compound

HRID 1096155Notes

Reaction equation

HRID 1096155 reaction equation
C(Cl)(=O)C(Cl)=O.[N:7]1([C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=2)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[NH2:22][C:23]1[C:24]2[CH:35]=[C:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[S:33][C:25]=2[N:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=1.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C=O>[N:7]1([C:13]2[CH:14]=[CH:15][C:16]([C:17]([NH:22][C:23]3[C:24]4[CH:35]=[C:34]([C:36]([O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:37])[S:33][C:25]=4[N:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=3)=[O:19])=[CH:20][CH:21]=2)[CH2:8][CH2:9][O:10][CH2:11][CH2:12]1

Participants

8

Reactant 5

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 3452784-(Morpholin-4-yl)benzoic acidHCID 516892Sodium BicarbonateHCID 577372725-tert-butyl 1-ethyl 3-amino-1H-thieno[2,3-c]pyrazole-1,5-dicarboxylate

Product 1

HCID 66784763HCID 66784763, compoundYield 41.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
5 °C

Procedure

Oxalyl chloride (20.2 mL, 231 mmol) was added to a suspension of 4-morpholin-4-ylbenzoic acid (7.98 g, 38.5 mmol) in dry dichloromethane (DCM, 210 mL) and dimethylformamide (DMF, 0.04 mL). After refluxing the mixture for 6.5 hours, volatiles were carefully removed under reduced pressure (taking up the residue three times with toluene). The resulting 4-morpholin-4-ylbenzoyl chloride hydrochloride was added portion-wise (in about 0.5 hours) to a suspension of 5-tert-butyl 1-ethyl 3-amino-1H-thieno[2,3-c]pyrazole-1,5-dicarboxylate (6.0 g, 19.3 mmol) in dry DCM (200 mL) and pyridine (23.2 mL, 289 mmol), under stirring at 5° C. The resulting suspension was stirred for 20 hours at room temperature. 300 mL of DCM and 300 mL of aqueous sodium bicarbonate were then added to the reaction mixture; the organic layer was separated, washed with brine, dried over sodium sulphate and evaporated. Purification by chromatography (DCM/ethyl acetate 7:3) gave 4.05 g of the title compound.

Workup

  1. temperatureAfter refluxing the mixture for 6.5 hours
  2. customvolatiles were carefully removed under reduced pressure (
  3. additionThe resulting 4-morpholin-4-ylbenzoyl chloride hydrochloride was added portion-wise (in about 0.5 hours)
  4. stirringThe resulting suspension was stirred for 20 hours at room temperature
  5. customthe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over sodium sulphate
  8. customevaporated
  9. customPurification by chromatography (DCM/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-2dd7ec9e92f54b58b0e65b5f67f16da6
Source dataset
uspto-grants-2012_03
Patent number
US08138217B2

Reaction notes

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