Hydrochloric Acid → HCID 59242116, compound

HRID 1876170Notes

Reaction equation

HRID 1876170 reaction equation
[Cl:1][CH:2]1[N:11]=[C:10](Cl)[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[NH:3]1.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([NH:19][CH3:20])=[CH:17][CH:16]=1.Cl>C(O)(C)C>[Cl:1][C:2]1[N:11]=[C:10]([N:19]([C:18]2[CH:21]=[CH:22][C:15]([O:14][CH3:13])=[CH:16][CH:17]=2)[CH3:20])[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 22250N-Methyl-4-anisidineHCID 68521080HCID 68521080, compound

Product 1

HCID 59242116HCID 59242116, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 2-methoxylcarbonyl cyclohexanone 5.00 g (455 mmol) and urea 6.00 g (100.0 mmol) with 2 mL of ethanol was stirred for 48 h under reflux. After cooling, the formed crude product was washed with water and dried in vacuo to give ca.4 g of 5,6,7,8-tetrahydro-1H-quinazoline-2,4-dione. A mixture of 5,6,7,8-tetrahydro-1H-quinazoline-2,4-dione 2.00 g (12.0 mmol) and POCl3 10 mL was stirred under reflux for 3 h. After cooling, excess of POCl3 was removed under reduced pressure, and the crude product was diluted with CHCl3, which was poured into ice-water, washed with water, and dried on anhydrous MgSO4. Removal of CHCl3 gave 2,4-dichloro-5,6,7,8-tetrahydro-1H-quinazoline in 95% yield. A solution of 2,4-dichloro-5,6,7,8-tetrahydro-1H-quinazoline 0.615 g (3.0 mmol) and 4-methoxy-N-methylaniline 0.411 g (1.0 mmol) with conc. HCl 0.5 mL in iso-propanol 30 mL was stirred at 23° C. for 16 h. The solution was concentrated under reduced pressure, diluted with CH2Cl2 30 mL, washed with sat. Na2CO3 aqueous solution, and dried on anhydrous MgSO4. After removal of solvents, the crude product was purified with gradient column chromatography (EtOAc/hexanes, 0% to 60%) to give titled product in 50% yield, which was further purified with preparative HPLC to give the corresponding TFA salt. 1H NMR (CDCl3, 400 MHz): δ 7.02 (d, 2H, J=9.0 Hz), 6.86 (d, 2H, J=9.0 Hz), 3.83 (s, 3H), 3.40 (s, 3H), 2.73 (t, 2H, J=6.7 Hz), 1.62-1.68 (m, 4H), 1.44-1.49 (m, 2H). m/z: 304.1236 (M+1).

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. additiondiluted with CH2Cl2 30 mL
  3. washwashed with sat. Na2CO3 aqueous solution
  4. dry with materialdried on anhydrous MgSO4
  5. customAfter removal of solvents
  6. customthe crude product was purified with gradient column chromatography (EtOAc/hexanes, 0% to 60%)

Sources & evidence

ORD record
ord-5a096328daf644c1af77d298884b0911
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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