Methyl Anthranilate → 5-(5-cyclopropyl-2H-pyrazol-3-ylamino)-1,2,3,4-tetrahydro-quinazolino[3,2-a]quinazolin-12-one hydrochloride

HRID 2264385Notes

Reaction equation

HRID 2264385 reaction equation
[Cl:1][CH:2]1[N:11]=[C:10]([NH:12][C:13]2[NH:14][N:15]=[C:16]([CH:18]3[CH2:20][CH2:19]3)[CH:17]=2)[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[NH:3]1.[C:21](OC)(=[O:29])[C:22]1[C:23](=[CH:25][CH:26]=[CH:27][CH:28]=1)[NH2:24].C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>CO.ClCCl.Cl.CO>[ClH:1].[CH:18]1([C:16]2[CH:17]=[C:13]([NH:12][C:10]3[C:9]4[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=4[N:3]4[C:21](=[O:29])[C:22]5[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=5[N:24]=[C:2]4[N:11]=3)[NH:14][N:15]=2)[CH2:20][CH2:19]1

Participants

8

Reactant 4

HCID 8635Methyl AnthranilateHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 178478382HCID 178478382, compound

Product 1

HCID 1784796005-(5-cyclopropyl-2H-pyrazol-3-ylamino)-1,2,3,4-tetrahydro-quinazolino[3,2-a]quinazolin-12-one hydrochlorideYield 7.1%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

(2-Chloro-1,2,5,6,7,8-hexahydro-quinazolin-4-yl)-(5-cyclopropyl-2H-pyrazol-3-yl)-amine (150 mg, 0.518 mmol), in methyl anthranilate (0.1 ml, 0.777 mmol) was heated to 135° C. for 4 hours to give a brown gum. This was dissolved in methanol/dichloromethane and added to a mixture of ethyl acetate and aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate and the extracts dried over magnesium sulphate and concentrated. Purification by flash chromatography on silica gel eluting with 4% methanol/dichloromethane gave a pale yellow gum. This was dissolved in 0.5M HCl in methanol and crystallised by the dropwise addition of diethyl ether to give cream coloured crystals of 5-(5-cyclopropyl-2H-pyrazol-3-ylamino)-1,2,3,4-tetrahydro-quinazolino[3,2-a]quinazolin-12-one hydrochloride (15 mg, 7%).

Workup

  1. customto give a brown gum
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialthe extracts dried over magnesium sulphate
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel eluting with 4% methanol/dichloromethane
  6. customgave a pale yellow gum
  7. customcrystallised by the dropwise addition of diethyl ether

Sources & evidence

ORD record
ord-47c08bc104eb44ab87618a6b59789872
Source dataset
uspto-grants-2010_12
Patent number
US07855214B2

Reaction notes

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