p-Toluenesulfonic acid monohydrate → HCID 136248829, compound

HRID 922358Notes

Reaction equation

HRID 922358 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[C:12]([CH:15]=[C:16]([O:18][CH3:19])[CH:17]=2)[CH:13]=O)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[NH2:20][C:21]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[C:26]([O:32][CH3:33])[C:22]=1[C:23]([NH2:25])=[O:24].OS([O-])=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[C:12]([C:13]3[NH:25][C:23](=[O:24])[C:22]4[C:21](=[CH:29][C:28]([O:30][CH3:31])=[CH:27][C:26]=4[O:32][CH3:33])[N:20]=3)[CH:15]=[C:16]([O:18][CH3:19])[CH:17]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86719340HCID 86719340, compound

Product 1

HCID 136248829HCID 136248829, compoundYield 79.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-(4-isopropylpiperazin-1-yl)-5-methoxybenzaldehyde (1.23 g, 4.68 mmol) in N,N-dimethylacetamide (20 mL) was added 2-amino-4,6-dimethoxybenzamide (0.59 g, 3.00 mmol), NaHSO3 (58.5 wt %, 0.87 g, 4.80 mmol) and p-toluenesulfonic acid monohydrate (1.82 g, 9.60 mmol). The reaction mixture was stirred at 120° C. for 20 h under nitrogen. After that time the reaction was cooled to rt and concentrated under reduced pressure. The residue was diluted with saturated Na2CO3 solution to adjust the pH to 12. The precipitated solids were collected by filtration, washed with water and dried under vacuum. The product was purified by flash column chromatography (silica gel, 86:10:4 dichloromethane/ethyl acetate/methanol followed by 86:10:4 dichloromethane/ethyl acetate/7 N NH3 in methanol) and prep. HPLC to give 2-(3-(4-isopropylpiperazin-1-yl)-5-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (1.04 g, 50%) as a white solid: mp 212-213° C.; 1H NMR (400 MHz, DMSO-d6): δ 11.99 (s, 1H), 7.36 (s, 1H), 7.20 (s, 1H), 6.76 (d, J=2.34 Hz, 1H), 6.60 (t, J=1.95 Hz, 1H), 6.53 (d, J=1.95 Hz, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.81 (s, 3H), 3.22 (t, J=4.29 Hz, 4H), 2.68 (quin, J=6.54 Hz, 1H), 2.58 (t, J=4.68 Hz, 4H), 1.01 (d, J=6.63 Hz, 6H); ESI MS m/z 437 [M−H]−.

Workup

  1. temperatureAfter that time the reaction was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with saturated Na2CO3 solution
  4. filtrationThe precipitated solids were collected by filtration
  5. washwashed with water
  6. customdried under vacuum
  7. customThe product was purified by flash column chromatography (silica gel, 86:10:4 dichloromethane/ethyl acetate/methanol followed by 86:10:4 dichloromethane/ethyl acetate/7 N NH3 in methanol)

Sources & evidence

ORD record
ord-abc1fe1dba0a4d2f930e368d4d953422
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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