HCID 86621925, compound → HCID 86621926, compound

HRID 1498752Notes

Reaction equation

HRID 1498752 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([CH2:16][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[C:10]([O:23][CH3:24])[C:9]=1[C:25](=[O:27])[NH2:26])(C)(C)C>CC(O)=O.Cl>[NH2:7][C:8]1[C:9]([C:25]([NH2:26])=[O:27])=[C:10]([O:23][CH3:24])[C:11]([CH2:16][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[C:12]([O:14][CH3:15])[CH:13]=1

Participants

4

Reactant 1

HCID 86621925HCID 86621925, compound

Product 1

HCID 86621926HCID 86621926, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolvent

Procedure

A solution of 6-tert-butoxycarbonylamino-2,4-dimethoxy-3-morpholin-4-ylmethyl-benzoic acid (1.8 g, 4.54 mmol), EDCl.HCl (1.31 g, 6.82 mmol), HOBt (1.23 g, 9.09 mmol), and triethylamine (3.3 mL, 23.7 mmol) in THF (50 mL) was stirred at room temperature for 1 h. Ammonium hydroxide (50% aqueous, 10 mL) was then added to the reaction mixture. The resulting mixture was stirred at room temperature for 6 h. The reaction was quenched by adding water (50 mL), extracted with DCM (3×100 mL), and concentrated using a rotary evaporator. The residue was further purified by column (SiO2, DCM/MeOH/EtOAc=2:1:4) to provide 0.9 g of (2-carbamoyl-3,5-dimethoxy-4-morpholin-4-ylmethyl-phenyl)-carbamic acid tert-butyl ester (50%). A solution of (2-carbamoyl-3,5-dimethoxy-4-morpholin-4-ylmethyl-phenyl)-carbamic acid tert-butyl ester (0.9 g, 2.74 mmol) in HOAc (20 mL) and 12 N HCl aqueous (20 mL) was stirred at 50° C. for 1 h and then concentrated to dryness using a rotary evaporator. The residue was mixed with saturated sodium bicarbonate aqueous (40 mL), extracted with DCM (3×100 mL), and concentrated. The residue was further purified by column (SiO2, DCM/MeOH/EtOAc=3:2:3) to provide 0.6 g of 6-amino-2,4-dimethoxy-3-morpholin-4-ylmethyl-benzamide (89%). A mixture of 6-amino-2,4-dimethoxy-3-morpholin-4-ylmethyl-benzamide (0.6 g, 2.03 mmol), 3,5-dimethyl-4-hydroxy benzaldehyde (0.61 g, 4.06 mmol), sodium hydrogensulfite (1.24 g, 7.0 mmol) and p-toluenesulfonic acid (1.14 g, 6 mmol) in N,N-dimethyl acetamide (20 mL) was stirred at 115° C. for 6 h. The reaction mixture was cooled to room temperature, diluted with water (50 mL), extracted with EtOAc, and concentrated. Purification by column chromatography afforded a solid residue, which was made into slurry in a mixed solvent of DCM-hexanes (3 mL-20 mL). The slurry was filtered and washed with hexanes to provide 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-6-(morpholinomethyl)quinazolin-4(3H)-one (56 mg, 6.6%) as a light yellow solid. Selected data: MS (ES) m/z: 426.0; MP 237.0-239.1° C.

Workup

  1. concentrationconcentrated to dryness
  2. customa rotary evaporator
  3. additionThe residue was mixed with saturated sodium bicarbonate aqueous (40 mL)
  4. extractionextracted with DCM (3×100 mL)
  5. concentrationconcentrated
  6. customThe residue was further purified by column (SiO2, DCM/MeOH/EtOAc=3:2:3)

Sources & evidence

ORD record
ord-e8e2405fb2e345e9a6a26b1d1ab5dad6
Source dataset
uspto-grants-2015_12
Patent number
US09199990B2

Reaction notes

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